Heart Failure NYHA Class III
Conditions
Keywords
Heart Failure, Heart Disease, Cardiovascular Disease, Pulmonary Artery Pressure
Brief summary
This is a prospective, open- label, single arm, multicenter clinical trial to evaluate the safety and effectiveness of the Cordella PA Sensor System in NYHA Class III Heart Failure Patients compared to a Performance Goal (PG).
Interventions
The Cordella PA Sensor System (CorPASS) is intended to measure, record, and transmit pulmonary artery pressure (PAP) data from NYHA Class III heart failure patients at home to clinicians for assessment and patient-centered heart failure management and comprises of seven subsystems that operate together to take daily Pulmonary Artery Pressure (PAP) readings at a patient's home and transmit the results to a care provider for evaluation. 1. Cordella Sensor 2. Cordella Delivery System 3. myCordella Patient Reader 4. Reader Dock 5. Cordella Calibration Equipment (CalEQ) 6. myCordella Hub 7. Cordella Data Analysis Platform (CDAP)
Sponsors
Endotronix, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject has given written informed consent 2. Male or female, at least 18 years of age 3. Diagnosis and treatment of HF (regardless of left ventricular ejection fraction (LVEF)) for ≥ 3 months and NYHA Class III HF at time of Screening 4. Subjects should be on stable, optimally titrated medical therapy for at least 30 days, as recommended according to current American Heart Association (AHA)/American College of Cardiology (ACC) guidelines as standard-of-care for HF therapy in the United States, or current European Society of Cardiology (ESC) guidelines for HF treatment in Europe, with any intolerance documented. 5. HF related hospitalization, HF treatment in a hospital day-care setting, or urgent outpatient clinic HF visit for IV diuretics within 12 month (last hospitalization should be 30 days before Screening/Enrollment) and/or N-terminal pro B-type Natriuretic Peptide (NT proBNP) at time of Screening/ Enrollment defined as: 1. Subjects with LVEF ≤ 50%: NT-proBNP ≥ 1500 pg/mL. 2. Subjects with LVEF \> 50%: NT-proBNP ≥ 800 pg/mL . Thresholds for NT-proBNP (for both LVEF ≤ 50% and LVEF \> 50%) will be corrected for body mass index (BMI) using a 4% reduction per BMI unit over 25 kg/m2 6. Subjects should be on diuretic therapy 7. Subjects who are physically able to hold the myCordella™ Patient Reader unit (approximate weight 1.3lb) against the ventral thoracic surface for up to 2 minutes per day while in a seated position, as well as dock and undock the myCordella™ Patient Reader 8. Subjects with sufficient eyesight, hearing, and mental capacity to respond to the myCordella™ Patient Reader's audio/visual cues and operate the myCordella™ Patient Reader 9. Subject has sufficient Cellular and/ or Wi- Fi Internet coverage at home 10. Subject agrees to return to the treating Investigator for all scheduled follow up visits and can return to the hospital for follow up
Exclusion criteria
1. Intolerance to all neuro-hormonal antagonists (i.e., intolerance to ACE-I, ARB, ARNI, and beta-blockers) due to hypotension or renal dysfunction 2. ACC/AHA Stage D refractory HF (including having received or currently receiving pharmacologic circulatory support with inotropes) 3. Subjects with history of recurrent pulmonary embolism ( ≥2 episodes within 5 years prior to Screening Visit) and/or deep vein thrombosis (\< 3 month prior to Screening Visit) 4. Subjects who have had a major cardiovascular (CV) event (e.g. myocardial infarction, stroke) within 3 months of the Screening Visit 5. Unrepaired severe valvular disease 6. Subjects with significant congenital heart disease that has not been repaired and would prevent implantation of the Cordella PA sensor or mechanical/tissue right heart valve(s) 7. Subjects with known coagulation disorders 8. Subjects with a hypersensitivity or allergy to platelet aggregation inhibitors including aspirin, clopidogrel, prasugrel, and ticagrelor; or patients unable to take dual antiplatelet or anticoagulants for one-month post implant 9. Known history of life threatening allergy to contrast dye 10. Subjects whereby RHC is contraindicated 11. Subjects with an active infection at the Sensor Implant Visit 12. Subjects with a Glomerular Filtration Rate (GFR) \<25 ml/min or who are on chronic renal dialysis 13. Implanted with Cardiac Resynchronization Therapy (CRT)-Pacemaker (CRT-P) or CRT-Defibrillator (CRT-D) for less than 90 days prior to screening visit 14. Received or are likely to receive an advanced therapy (e.g. mechanical circulatory support or lung or heart transplant) in the next 12 months 15. Subjects who are pregnant or breastfeeding 16. Subjects who are unwilling or deemed by the Investigator to be unwilling to comply with the study protocol, or subjects with a history of non-compliance 17. Severe illness, other than heart disease, which would limit survival to \<1 year 18. Subjects whose clinical condition, in the opinion of the Investigator, makes them an unsuitable candidate for the study 19. Subjects enrolled in another investigational trial with an active treatment arm 20. Subject who is in custody by order of an authority or a court of law
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy 6 Month Incidence of HF Related Hospitalizations (HFH) or All-cause Mortality | 6 months | The primary efficacy endpoint was the 6-month incidence of HF related hospitalizations or all-cause mortality in the modified Intent-to-Treat (mITT) population. As per the approved protocol/CIP, for study success the upper confidence bound of the observed event rate in the mITT population was required to be less than the performance goal (PG) of 0.43 events per patient 6-month, or equivalently, the corresponding p-value from the hypothesis test of 6-month incidence rate compared to PG was less than 0.025. Furthermore, the observed incidence rate was required to be less than 0.37. The 6-month incidence rate was derived using a Poisson regression with the number of events as the dependent variable and the exposure time as an offset term. In these analyses, a subject's exposure time was defined as the time to death, early study discontinuation, or 6 months (whichever occurred first). |
| Safety: Freedom From Device/System Related Complication | 6 months | A device/system related complication (DSRC) is defined as an AE that is, or is possibly, related to the device/system (Cordella PA Sensor or electronic components) and is either treated invasively (other than intramuscular medication or diagnostic RHC) or results in subject´s death or explant of the device. The first primary safety endpoint describes freedom from a DSRC through 6 months and was tested against the null rate of 90%. |
| Safety: Freedom From Pressure Sensor Failure | 6 months | A pressure sensor failure (PSF) occurs when the sensor malfunctions to the point that no readings can be obtained from the sensor after all attempts are exhausted including troubleshooting the system to rule out any problems with the electronic components. The second primary safety endpoint describes freedom from Pressure Sensor Failure through 6 months, it was tested against the null rate of 95%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HF Hospitalizations | 6 Months prior to implant and 6 months post implant | Number of HF Hospitalizations at 6 months post-implant compared to the number of HF Hospitalizations in the 6 months prior to implant |
| HF Hospitalizations or Emergency Department/Hospital Outpatient IV Diuretic Visits. | 6 months | Incidence rate of HF Hospitalizations, Emergency Department/ Hospital Outpatient IV diuretic visits of Former Control Arm and Modified Intent to Treat at 6 months post implant, added together with equal weighting into a total number of events. |
| Mortality | 6 Months | Cardiac and all-cause mortality |
| IV Diuretic Visits | 6 Months | Intravenous (IV) diuretic visits |
| Pulmonary Artery Pressure (PAP) | 6 months | Change in PAP: a. From Baseline through 6 months in subjects with a baseline mPAP i. above target range ii. within or below target range iii. Overall |
| Device Success | 6 Months | Proportion of device success as documented by ability of the System to successfully transmit PAP data transmit PAP data |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) | 6 Months | The Quality of Life KCCQ questionnaire is a measure of health-related quality of life. It is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life related to Heart Failure. From 23-items, the Overall Summary Score (OSS) will be calculated. In the OSS, each of the 23 items are converted onto a 0 to 100 scale using this formula: (Raw score - Minimum Raw Score)/(Maximum Raw Score - Minimum Raw Score) \* 100. Then these are averaged across the 23 items. A score of 100 (the maximum score) would indicate maximum quality of life relating to heart failure and a score of 0 (scale minimum) would indicate the worst possible quality of life relating to heart failure, with higher scores generally indicating higher quality of life. |
| NYHA | 6 Months | New York Heart Association (NYHA) Classification at 6 months. The New York Heart Association (NYHA) Classification provides a way of classifying the extent of heart failure by classifying patients in one of four categories based on their limitations during physical activity and in degree of shortness of breath and or angina pain. Class I is the least severe and Class IV is the most severe. The classes are: Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc. Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances. Comfortable only at rest. Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. |
| 6-Minute Walk Test | 6 Months | Functional status improvement, as measured by 6-Minute Walk Test total distance walked. The 6-Minute Walk Test (6MWT) is a test that measures the total distance an individual can walk on a flat, hard surface in 6 minutes. It is commonly used to evaluate functional exercise capacity in patients with conditions including heart failure. The minimum score possible is 0, which would represent an inability to walk any distance. There is no maximum score, as a patient could theoretically walk any distance in 6 minutes though 800 meters considered the top reference range, which is what would be expected by elite athletes. Higher score indicate greater higher exercise capacity and lower scores indicate lower exercise capacity. |
| Number and Percent of Patients With Serious Adverse Events | 6 Months | Number and percent of patients with serious adverse events throughout the study (site-reported). |
| Incidence of HF Hospitalizations or All-cause Mortality | 12 months | Incidence of HF Hospitalizations or all-cause mortality at 12 months calculated from Poisson regression. |
| N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) | 6 months | Change of N-terminal pro B-type Natriuretic Peptide (NT-proBNP) from Baseline through 6 months. NT-proBNP is a biomarker used to assess heart failure (HF). NT-proBNP levels vary widely and are reported in picograms per milliliter (pg/mL) or nanograms per liter (ng/L), with no predefined maximum value. Zero is a hypothetical minimum value though this is, in practice, not possible. In the current context, higher scores indicate more severe heart failure and lower levels indicate less severe heart failure. |
| Days Alive and Out of Hospital (DAOH) | 6 Months | Days Alive and Out of Hospital (DAOH) during the 6 months after implant |
| Number of Heart Failure Related Medication Changes | 6 Months | Number of patients (%) with heart failure related medication changes in the 6 months after implant |
| Number of HF Hospitalization or All-cause Mortality | 12 months | Number of HF Hospitalizations or all-cause mortality at 12 months |
| Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits, All-cause Mortality | 6 months | Number of combined outcome of: 1. First and recurrent Heart Failure Hospitalizations 2. Emergency Department / Hospital Outpatient IV diuretic visits all-cause mortality at 6 months, added together with equal weighting into a total number of events. |
| Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits | 6 months | Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV diuretic visits at 6 months. |
| Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events | 6 months | Frequency of implant procedure and procedure related adverse events and serious adverse events |
Countries
Belgium, Ireland, United States
Contacts
STUDY_DIRECTOREdward Karst
Edwards Lifesciences IHFM
Participant flow
Recruitment details
Enrollment was initiated on January 10, 2020, and completed on March 9, 2023, among 77 sites in the United States and five (5) sites in Ireland and Belgium. The last implant procedure was performed on March 31, 2023. The patient population consisted of male and female patients, ≥ 18 years of age with a diagnosis of NYHA Class III HF who met the study patient selection criteria.
Pre-assignment details
Of the 738 enrolled subjects, 528 received an implant, 125 had screen failure and 85 were withdrawn prior to implant. Of 85 withdrawn subjects, in 37 instances the implant procedure was aborted prior to deploying the implant. Of 528 subjects implanted, 72 were in the control group (eliminated in trial redesign). The remaining 456 patients form the mITT population, which was used for all efficacy analyses. All safety analyses used the ITT population (456 mITT + 37 withdrawn = 493 patients).
Participants by arm
| Arm | Count |
|---|---|
| Modified Intent-to-Treat (mITT) Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) and Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) using the Cordella Heart Failure System (CHFS) with the PA pressure sensor. Made up of open label arm plus former treatment arm.
Cordella™ Pulmonary Artery Sensor System: The Cordella PA Sensor System (CorPASS) is intended to measure, record, and transmit pulmonary artery pressure (PAP) data from NYHA Class III heart failure patients at home to clinicians for assessment and patient-centered heart failure management and comprises of seven subsystems that operate together to take daily Pulmonary Artery Pressure (PAP) readings at a patient's home and transmit the results to a care provider for evaluation.
1. Cordella Sensor
2. Cordella Delivery System
3. myCordella Patient Reader
4. Reader Dock
5. Cordella Calibration Equipment (CalEQ)
6. myCordella Hub
7. Cordella Data Analysis Platform (CDAP) | 456 |
| Former Control Arm Received standard of care heart failure management (i.e., Guideline Directed Medical Therapy) using the Cordella Heart Failure System (CHFS) excluding the PA pressure sensor until the trial redesign. After trial redesign were crossed over to receive standard of care HF management using the Cordella HF system with the PA pressure sensor. | 72 |
| Total | 528 |
Baseline characteristics
| Characteristic | Former Control Arm | Total | Modified Intent-to-Treat (mITT) |
|---|---|---|---|
| Age, Continuous | 65.9 Years STANDARD_DEVIATION 11.26 | 63.8 Years STANDARD_DEVIATION 12.4 | 63.5 Years STANDARD_DEVIATION 12.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 25 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 462 Participants | 401 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 41 Participants | 35 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 7 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 95 Participants | 84 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 16 Participants | 13 Participants |
| Race (NIH/OMB) White | 56 Participants | 403 Participants | 347 Participants |
| Region of Enrollment Belgium | 0 participants | 12 participants | 12 participants |
| Region of Enrollment Ireland | 0 participants | 6 participants | 6 participants |
| Region of Enrollment United States | 72 participants | 510 participants | 438 participants |
| Sex: Female, Male Female | 30 Participants | 210 Participants | 180 Participants |
| Sex: Female, Male Male | 42 Participants | 318 Participants | 276 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 33 / 493 | 5 / 72 |
| other Total, other adverse events | 379 / 493 | 60 / 72 |
| serious Total, serious adverse events | 278 / 493 | 47 / 72 |
Outcome results
Primary
Efficacy 6 Month Incidence of HF Related Hospitalizations (HFH) or All-cause Mortality
The primary efficacy endpoint was the 6-month incidence of HF related hospitalizations or all-cause mortality in the modified Intent-to-Treat (mITT) population. As per the approved protocol/CIP, for study success the upper confidence bound of the observed event rate in the mITT population was required to be less than the performance goal (PG) of 0.43 events per patient 6-month, or equivalently, the corresponding p-value from the hypothesis test of 6-month incidence rate compared to PG was less than 0.025. Furthermore, the observed incidence rate was required to be less than 0.37. The 6-month incidence rate was derived using a Poisson regression with the number of events as the dependent variable and the exposure time as an offset term. In these analyses, a subject's exposure time was defined as the time to death, early study discontinuation, or 6 months (whichever occurred first).
Time frame: 6 months
Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Arm and Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent-to-Treat (mITT) | Efficacy 6 Month Incidence of HF Related Hospitalizations (HFH) or All-cause Mortality | 0.1549 Events Per Patient Per 6 Months |
| Former Control Arm | Efficacy 6 Month Incidence of HF Related Hospitalizations (HFH) or All-cause Mortality | 0.2787 Events Per Patient Per 6 Months |
p-value: <0.0001Poisson Regression
Primary
Safety: Freedom From Device/System Related Complication
A device/system related complication (DSRC) is defined as an AE that is, or is possibly, related to the device/system (Cordella PA Sensor or electronic components) and is either treated invasively (other than intramuscular medication or diagnostic RHC) or results in subject´s death or explant of the device. The first primary safety endpoint describes freedom from a DSRC through 6 months and was tested against the null rate of 90%.
Time frame: 6 months
Population: The Intent-to-Treat Population (ITT) includes all enrolled subjects intended to receive the Cordella PA Sensor who entered the Cath Lab, including those in whom Implant Procedure was not attempted for whatever reason (e.g., Cordella PA Sensor Implant cannot be performed due to anatomical reasons) from the Open Label Arm and Former Treatment Arm. Patients in this population in whom the Cordella PA Sensor Implant was not attempted were followed through 30 days for safety purposes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent-to-Treat (mITT) | Safety: Freedom From Device/System Related Complication | 0.992 Proportion of patients without a DSRC |
| Former Control Arm | Safety: Freedom From Device/System Related Complication | 0.986 Proportion of patients without a DSRC |
Primary
Safety: Freedom From Pressure Sensor Failure
A pressure sensor failure (PSF) occurs when the sensor malfunctions to the point that no readings can be obtained from the sensor after all attempts are exhausted including troubleshooting the system to rule out any problems with the electronic components. The second primary safety endpoint describes freedom from Pressure Sensor Failure through 6 months, it was tested against the null rate of 95%.
Time frame: 6 months
Population: The Intent-to-Treat Population (ITT) includes all enrolled subjects intended to receive the Cordella PA Sensor who entered the Cath Lab, including those in whom Implant Procedure was not attempted for whatever reason (e.g., Cordella PA Sensor Implant cannot be performed due to anatomical reasons) from the Open Label Arm and Former Treatment Arm. Patients in this population in whom the Cordella PA Sensor Implant was not attempted were followed through 30 days for safety purposes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent-to-Treat (mITT) | Safety: Freedom From Pressure Sensor Failure | 0.998 Proportion of patients without a PSF |
| Former Control Arm | Safety: Freedom From Pressure Sensor Failure | 1.000 Proportion of patients without a PSF |
Secondary
6-Minute Walk Test
Functional status improvement, as measured by 6-Minute Walk Test total distance walked. The 6-Minute Walk Test (6MWT) is a test that measures the total distance an individual can walk on a flat, hard surface in 6 minutes. It is commonly used to evaluate functional exercise capacity in patients with conditions including heart failure. The minimum score possible is 0, which would represent an inability to walk any distance. There is no maximum score, as a patient could theoretically walk any distance in 6 minutes though 800 meters considered the top reference range, which is what would be expected by elite athletes. Higher score indicate greater higher exercise capacity and lower scores indicate lower exercise capacity.
Time frame: 6 Months
Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT. For this measure, only patients who completed the measure were included in the results reported, which is the reason for the smaller number of participants in these results than in the mITT population overall.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Modified Intent-to-Treat (mITT) | 6-Minute Walk Test | Baseline | 259.5 Meters Walked | Standard Deviation 121.1 |
| Modified Intent-to-Treat (mITT) | 6-Minute Walk Test | 6 Months | 283.2 Meters Walked | Standard Deviation 123.9 |
| Former Control Arm | 6-Minute Walk Test | Baseline | 281.5 Meters Walked | Standard Deviation 133.6 |
| Former Control Arm | 6-Minute Walk Test | 6 Months | 299.4 Meters Walked | Standard Deviation 147.5 |
p-value: 0.1086Wilcoxon (Mann-Whitney)
Secondary
Days Alive and Out of Hospital (DAOH)
Days Alive and Out of Hospital (DAOH) during the 6 months after implant
Time frame: 6 Months
Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Modified Intent-to-Treat (mITT) | Days Alive and Out of Hospital (DAOH) | 172.0 days | Standard Deviation 27.2 |
| Former Control Arm | Days Alive and Out of Hospital (DAOH) | 173.7 days | Standard Deviation 19.6 |
Secondary
Device Success
Proportion of device success as documented by ability of the System to successfully transmit PAP data transmit PAP data
Time frame: 6 Months
Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent-to-Treat (mITT) | Device Success | 0.991 Proportion of device readings successful |
Secondary
HF Hospitalizations
Number of HF Hospitalizations at 6 months post-implant compared to the number of HF Hospitalizations in the 6 months prior to implant
Time frame: 6 Months prior to implant and 6 months post implant
Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Arm and Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Modified Intent-to-Treat (mITT) | HF Hospitalizations | Total HF Hospitalizations events in 6 months before implant | 266 events |
| Modified Intent-to-Treat (mITT) | HF Hospitalizations | Total HF Hospitalizations events in 6 months after implant | 60 events |
| Former Control Arm | HF Hospitalizations | Total HF Hospitalizations events in 6 months before implant | 36 events |
| Former Control Arm | HF Hospitalizations | Total HF Hospitalizations events in 6 months after implant | 18 events |
Comparison: Comparison of HF Hospitalization events 6 months before implant vs 6 months after implantp-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
HF Hospitalizations or Emergency Department/Hospital Outpatient IV Diuretic Visits.
Incidence rate of HF Hospitalizations, Emergency Department/ Hospital Outpatient IV diuretic visits of Former Control Arm and Modified Intent to Treat at 6 months post implant, added together with equal weighting into a total number of events.
Time frame: 6 months
Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent-to-Treat (mITT) | HF Hospitalizations or Emergency Department/Hospital Outpatient IV Diuretic Visits. | 0.1703 Events Per Patient Per 6 Months |
| Former Control Arm | HF Hospitalizations or Emergency Department/Hospital Outpatient IV Diuretic Visits. | 0.2508 Events Per Patient Per 6 Months |
p-value: 0.0697Poisson Regression
Secondary
Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events
Frequency of implant procedure and procedure related adverse events and serious adverse events
Time frame: 6 months
Population: The Intent-to-Treat Population (ITT) includes all implanted subjects from the Open Label Arm and Former Treatment Arm. All safety analyses were performed on the ITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Modified Intent-to-Treat (mITT) | Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events | Subjects with at least one predefined AE or SAE with study device or implant procedure relationship | 36 Participants |
| Modified Intent-to-Treat (mITT) | Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events | Bleeding | 3 Participants |
| Modified Intent-to-Treat (mITT) | Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events | Conduction Disturbances and Arrhythmias | 4 Participants |
| Modified Intent-to-Treat (mITT) | Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events | Heart Failure | 2 Participants |
| Modified Intent-to-Treat (mITT) | Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events | Hemoptysis | 14 Participants |
| Modified Intent-to-Treat (mITT) | Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events | Pulmonary Embolism | 1 Participants |
| Modified Intent-to-Treat (mITT) | Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events | Vascular Access Site and Access-Related Complications | 12 Participants |
| Modified Intent-to-Treat (mITT) | Implant Procedure and Procedure Related Adverse Events and Serious Adverse Events | Other | 16 Participants |
Secondary
Incidence of HF Hospitalizations or All-cause Mortality
Incidence of HF Hospitalizations or all-cause mortality at 12 months calculated from Poisson regression.
Time frame: 12 months
Population: Participants who received Cordella PA sensor implant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent-to-Treat (mITT) | Incidence of HF Hospitalizations or All-cause Mortality | 0.3629 Events Per Patient Per 12 Months |
| Former Control Arm | Incidence of HF Hospitalizations or All-cause Mortality | 0.5438 Events Per Patient Per 12 Months |
Secondary
IV Diuretic Visits
Intravenous (IV) diuretic visits
Time frame: 6 Months
Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent-to-Treat (mITT) | IV Diuretic Visits | 17 events |
| Former Control Arm | IV Diuretic Visits | 0 events |
Secondary
Kansas City Cardiomyopathy Questionnaire (KCCQ)
The Quality of Life KCCQ questionnaire is a measure of health-related quality of life. It is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life related to Heart Failure. From 23-items, the Overall Summary Score (OSS) will be calculated. In the OSS, each of the 23 items are converted onto a 0 to 100 scale using this formula: (Raw score - Minimum Raw Score)/(Maximum Raw Score - Minimum Raw Score) \* 100. Then these are averaged across the 23 items. A score of 100 (the maximum score) would indicate maximum quality of life relating to heart failure and a score of 0 (scale minimum) would indicate the worst possible quality of life relating to heart failure, with higher scores generally indicating higher quality of life.
Time frame: 6 Months
Population: All primary and secondary effectiveness analyses are performed on the Modified Intent-to-Treat Population (mITT). For this measure, only patients who completed the measure were included in the results reported, which is the reason for the smaller number of patients in these results than in the mITT population overall.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Modified Intent-to-Treat (mITT) | Kansas City Cardiomyopathy Questionnaire (KCCQ) | Baseline | 52.8 points | Standard Deviation 22.8 |
| Modified Intent-to-Treat (mITT) | Kansas City Cardiomyopathy Questionnaire (KCCQ) | 6 Month | 57.8 points | Standard Deviation 24.2 |
| Former Control Arm | Kansas City Cardiomyopathy Questionnaire (KCCQ) | Baseline | 49.7 points | Standard Deviation 23.8 |
| Former Control Arm | Kansas City Cardiomyopathy Questionnaire (KCCQ) | 6 Month | 54.2 points | Standard Deviation 25.2 |
p-value: 0.0026Wilcoxon (Mann-Whitney)
Secondary
Mortality
Cardiac and all-cause mortality
Time frame: 6 Months
Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Modified Intent-to-Treat (mITT) | Mortality | All-cause Mortality | 10 Participants |
| Modified Intent-to-Treat (mITT) | Mortality | Cardiac Mortality | 6 Participants |
| Former Control Arm | Mortality | All-cause Mortality | 2 Participants |
| Former Control Arm | Mortality | Cardiac Mortality | 2 Participants |
Secondary
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
Change of N-terminal pro B-type Natriuretic Peptide (NT-proBNP) from Baseline through 6 months. NT-proBNP is a biomarker used to assess heart failure (HF). NT-proBNP levels vary widely and are reported in picograms per milliliter (pg/mL) or nanograms per liter (ng/L), with no predefined maximum value. Zero is a hypothetical minimum value though this is, in practice, not possible. In the current context, higher scores indicate more severe heart failure and lower levels indicate less severe heart failure.
Time frame: 6 months
Population: All primary and secondary effectiveness analyses are performed on the Modified Intent-to-Treat Population (mITT). For this measure, only patients who completed the measure were included in the results reported, which is the reason for the smaller number of patients in these results than in the mITT population overall.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Modified Intent-to-Treat (mITT) | N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) | Baseline | 1731.4 pg/ml | Standard Deviation 3012.8 |
| Modified Intent-to-Treat (mITT) | N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) | 6 Months | 1632.5 pg/ml | Standard Deviation 2742.4 |
| Former Control Arm | N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) | Baseline | 1786.8 pg/ml | Standard Deviation 3809.4 |
| Former Control Arm | N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) | 6 Months | 1345.6 pg/ml | Standard Deviation 2435.7 |
p-value: 0.0628Wilcoxon (Mann-Whitney)
Secondary
Number and Percent of Patients With Serious Adverse Events
Number and percent of patients with serious adverse events throughout the study (site-reported).
Time frame: 6 Months
Population: The Intent-to-Treat Population (ITT) includes all implanted subjects from the Open Label Arm and Former Treatment Arm. All safety analyses were performed on the ITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Subjects with at least one predefined SAE | 196 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Vascular Access Site and Access-Related Complications | 4 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Heart Failure | 79 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | ED Visit | 4 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Hospitalization | 72 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Urgent, Unscheduled Outpatient Office/ Practice | 2 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Acute Kidney Injury (AKIN) | 22 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Bleeding | 6 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Conduction Disturbances and Arrhythmias | 28 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Hemoptysis | 12 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Myocardial Infarction (MI) | 3 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Pulmonary Embolism | 6 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Pulmonary Occlusion | 0 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Renal Dysfunction | 8 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Stroke and Trans Ischemic Attach (TIA) | 0 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Vessel Trauma | 4 Participants |
| Modified Intent-to-Treat (mITT) | Number and Percent of Patients With Serious Adverse Events | Other | 123 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Renal Dysfunction | 1 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Hemoptysis | 1 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Heart Failure | 16 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Subjects with at least one predefined SAE | 31 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Vessel Trauma | 0 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Myocardial Infarction (MI) | 1 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | ED Visit | 0 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Stroke and Trans Ischemic Attach (TIA) | 1 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Hospitalization | 16 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Pulmonary Embolism | 0 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Urgent, Unscheduled Outpatient Office/ Practice | 0 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Vascular Access Site and Access-Related Complications | 2 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Acute Kidney Injury (AKIN) | 7 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Pulmonary Occlusion | 0 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Bleeding | 4 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Other | 17 Participants |
| Former Control Arm | Number and Percent of Patients With Serious Adverse Events | Conduction Disturbances and Arrhythmias | 4 Participants |
Secondary
Number of Heart Failure Related Medication Changes
Number of patients (%) with heart failure related medication changes in the 6 months after implant
Time frame: 6 Months
Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Modified Intent-to-Treat (mITT) | Number of Heart Failure Related Medication Changes | Baseline to 1 Month | 234 Participants |
| Modified Intent-to-Treat (mITT) | Number of Heart Failure Related Medication Changes | 1 Month to 3 Months | 227 Participants |
| Modified Intent-to-Treat (mITT) | Number of Heart Failure Related Medication Changes | 3 Months to 6 Months | 260 Participants |
| Former Control Arm | Number of Heart Failure Related Medication Changes | Baseline to 1 Month | 25 Participants |
| Former Control Arm | Number of Heart Failure Related Medication Changes | 1 Month to 3 Months | 25 Participants |
| Former Control Arm | Number of Heart Failure Related Medication Changes | 3 Months to 6 Months | 32 Participants |
Secondary
Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits
Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV diuretic visits at 6 months.
Time frame: 6 months
Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent-to-Treat (mITT) | Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits | 77 Events |
| Former Control Arm | Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits | 18 Events |
| Within/BelowTarget mPAP at Baseline | Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits | 15 Events |
| Open Label Arm | Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits | 62 Events |
Secondary
Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits, All-cause Mortality
Number of combined outcome of: 1. First and recurrent Heart Failure Hospitalizations 2. Emergency Department / Hospital Outpatient IV diuretic visits all-cause mortality at 6 months, added together with equal weighting into a total number of events.
Time frame: 6 months
Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Intent-to-Treat (mITT) | Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits, All-cause Mortality | 87 events |
| Former Control Arm | Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits, All-cause Mortality | 20 events |
| Within/BelowTarget mPAP at Baseline | Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits, All-cause Mortality | 17 events |
| Open Label Arm | Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits, All-cause Mortality | 70 events |
Secondary
Number of HF Hospitalization or All-cause Mortality
Number of HF Hospitalizations or all-cause mortality at 12 months
Time frame: 12 months
Population: Participants who received the Cordella PA sensor implant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Modified Intent-to-Treat (mITT) | Number of HF Hospitalization or All-cause Mortality | Heart Failure Hospitilizations | 126 Events |
| Modified Intent-to-Treat (mITT) | Number of HF Hospitalization or All-cause Mortality | All-Cause Deaths | 33 Events |
| Former Control Arm | Number of HF Hospitalization or All-cause Mortality | Heart Failure Hospitilizations | 33 Events |
| Former Control Arm | Number of HF Hospitalization or All-cause Mortality | All-Cause Deaths | 5 Events |
Secondary
NYHA
New York Heart Association (NYHA) Classification at 6 months. The New York Heart Association (NYHA) Classification provides a way of classifying the extent of heart failure by classifying patients in one of four categories based on their limitations during physical activity and in degree of shortness of breath and or angina pain. Class I is the least severe and Class IV is the most severe. The classes are: Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc. Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances. Comfortable only at rest. Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.
Time frame: 6 Months
Population: All primary and secondary effectiveness analyses are performed on the Modified Intent-to-Treat Population (mITT). For this measure, only patients who completed the measure were included in the results reported, which is the reason for the smaller number of patients in these results than in the mITT population overall.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Modified Intent-to-Treat (mITT) | NYHA | I | 23 Participants |
| Modified Intent-to-Treat (mITT) | NYHA | II | 121 Participants |
| Modified Intent-to-Treat (mITT) | NYHA | III | 262 Participants |
| Modified Intent-to-Treat (mITT) | NYHA | IV | 8 Participants |
| Former Control Arm | NYHA | IV | 0 Participants |
| Former Control Arm | NYHA | I | 3 Participants |
| Former Control Arm | NYHA | III | 46 Participants |
| Former Control Arm | NYHA | II | 16 Participants |
Comparison: The New York Heart Association (NYHA) Classification is a system used to evaluate and classify the severity of heart failure based on symptoms, patient's physical activity, and quality of life. Its scale ranges from class 1 to 4 with class 1 indicating the least severe heart failure symptoms (i.e., the best functionality) and class 4 indicating the most severe heart failure symptoms (i.e., the poorest functionality), with higher classes indicating poorer functioning as relates to heart failure.p-value: <0.0001Chi-squared
Secondary
Pulmonary Artery Pressure (PAP)
Change in PAP: a. From Baseline through 6 months in subjects with a baseline mPAP i. above target range ii. within or below target range iii. Overall
Time frame: 6 months
Population: The Modified Intent-to-Treat Population (mITT) includes all implanted subjects from the Open Label Armand Former Treatment Arm. All primary and secondary effectiveness analyses are performed on the mITT. mPAP target was 20 mmHG, thus patients above 20 mmHG for mPAP were assigned to Above Target group and patients at or below 20 mmHG mPAP were assigned to the Within/Below Target group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Modified Intent-to-Treat (mITT) | Pulmonary Artery Pressure (PAP) | Baseline | 20.2 mmHG of mPAP | Standard Deviation 10.3 |
| Modified Intent-to-Treat (mITT) | Pulmonary Artery Pressure (PAP) | 6 Months | 21.4 mmHG of mPAP | Standard Deviation 9.3 |
| Former Control Arm | Pulmonary Artery Pressure (PAP) | Baseline | 29.2 mmHG of mPAP | Standard Deviation 7.7 |
| Former Control Arm | Pulmonary Artery Pressure (PAP) | 6 Months | 26.8 mmHG of mPAP | Standard Deviation 9.2 |
| Within/BelowTarget mPAP at Baseline | Pulmonary Artery Pressure (PAP) | Baseline | 12.8 mmHG of mPAP | Standard Deviation 4.9 |
| Within/BelowTarget mPAP at Baseline | Pulmonary Artery Pressure (PAP) | 6 Months | 17.0 mmHG of mPAP | Standard Deviation 6.8 |
p-value: 0.0952Wilcoxon (Mann-Whitney)
p-value: 0.009Wilcoxon (Mann-Whitney)
p-value: <0.0001Wilcoxon (Mann-Whitney)