Heart Failure, Congestive
Conditions
Brief summary
This is a prospective, multi-center, randomized, single-blind clinical trial conducted in the United States (US). The objective of the study is to evaluate the safety and efficacy of the HF Pressure Measurement System in reducing heart failure (HF) related hospitalizations in a subset of subjects suffering from HF.
Interventions
DEVICEHF Pressure Measurement System
A pressure sensor is intended to be implanted into the pulmonary artery at the time of Swan-Ganz catheterization.
Sponsors
CardioMEMS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of HF ≥ 3 months, with either preserved or reduced LVEF 2. Diagnosis of NYHA Class III HF (historical assessment documented at screening visit) 3. Subjects with reduced LVEF must be receiving a beta blocker for 3 months and an ACE-I or ARB for one month unless in the investigator's opinion, the subject is intolerant to beta blockers, ACE-I or ARB. Beta blockers and ACE-I (or ARB) doses should be stable for one month prior to study entry. 4. At least 1 HF hospitalization within 12 months of Screening Visit 5. Subjects with pulmonary artery branch diameter sized between 7mm and 15mm (implanted vessel)
Exclusion criteria
1. Subjects with history of recurrent (\> 1) pulmonary embolism or deep vein thrombosis 2. Subjects, in the Investigator's opinion, unable to tolerate a right heart catheterization 3. Subjects who have had a major cardiovascular event (e.g., myocardial infarction, stroke) within 2 months of Screening Visit 4. Subjects with Cardiac Resynchronization Device (CRT) implanted ≤ 3 months prior to enrollment 5. Subjects with a Glomerular Filtration Rate (GFR) \<25 ml/min who are non-responsive to diuretic therapy or who are on chronic renal dialysis 6. Subjects likely to undergo heart transplantation within 6 months of Screening Visit 7. Subjects with congenital heart disease or mechanical right heart valve(s) 8. Subjects with known coagulation disorders 9. Subjects with a hypersensitivity or allergy to aspirin, and/or clopidogrel
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Freedom From a Device/System-related Complication (DSRC). | 6 months | A DSRC is an adverse event that is, or is possibly, related to the HF Pressure Measurement System and at least one the following: * is treated with invasive means (other than intramuscular medication or a right heart catheterization with a Swan-Ganz measurement which is used for diagnostic purposes) * results in the death of the subject * results in the explant of the device |
| Rate of Heart Failure Related (HFR) Hospitalizations | 6 months | — |
| Freedom From Pressure Sensor Failure | 6 months | A pressure sensor failure occurs when the sensor malfunctions to the point that no readings can be obtained from it after all attempts are exhausted including troubleshooting the system to rule out any problems with the electronic components. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life - Minnesota Living With Heart Failure Questionnaire (MLHFQ) | 6 months | THe MLHFQ is patient self-assessment of how heart failure affects his or her daily life. To measure the effects of symptoms, functional limitations, psychological distress on an individual's quality of life, the MLHFQ questionnaire asks each person to indicate using a 6-point, zero to five, Likert scale how much each of 21 facets prevented them from living as they desired. Total scores are provided as sums. The total score scale range is 0 - 105. A lower total score is indicative of better quality of life. |
| Days Alive Outside of the Hospital | 6 months | — |
| Change From Baseline in Pulmonary Artery Mean Pressure | 6 months | Change from baseline in pulmonary artery mean pressure was calculated using an area under the curve (AUC) methodology. All patients were instructed to take daily home readings for 180 days. By patient, a baseline average for the first 7 days of home readings was calculated. The difference between baseline and each daily reading was then determined and a corresponding daily AUC value was calculated. Finally, all daily AUC values were summed over the entire 180 day period resulting in a total AUC per patient. These data were aggregated for each randomization group and then compared. The unit of measure is mmHg x Days. |
| Proportion of Patients Hospitalized for Heart Failure | 6 months | — |
Other
| Measure | Time frame |
|---|---|
| Rate of HFR Hospitalizations | Study duration: average patient follow-up of 15 months |
| Freedom From Pressure Sensor Failure | Study duration: average patient follow-up of 15 months |
| Freedom From a Device/System-related Complication (DSRC) | Study duration: average patient follow-up of 15 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment TREATMENT group: standard of care HF management plus HF management based upon hemodynamic information obtained from the HF Pressure Measurement System | 270 |
| Control CONTROL group: standard of care HF management | 280 |
| Total | 550 |
Baseline characteristics
| Characteristic | Total | Treatment | Control |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 245 Participants | 120 Participants | 125 Participants |
| Age, Categorical Between 18 and 65 years | 305 Participants | 150 Participants | 155 Participants |
| Age, Continuous | 61.6 years STANDARD_DEVIATION 12.8 | 61.3 years STANDARD_DEVIATION 13 | 61.8 years STANDARD_DEVIATION 12.7 |
| Region of Enrollment United States | 550 participants | 270 participants | 280 participants |
| Sex: Female, Male Female | 151 Participants | 76 Participants | 75 Participants |
| Sex: Female, Male Male | 399 Participants | 194 Participants | 205 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 175 / 270 | 174 / 280 |
| serious Total, serious adverse events | 121 / 270 | 155 / 280 |
Outcome results
Primary
Freedom From a Device/System-related Complication (DSRC).
A DSRC is an adverse event that is, or is possibly, related to the HF Pressure Measurement System and at least one the following: * is treated with invasive means (other than intramuscular medication or a right heart catheterization with a Swan-Ganz measurement which is used for diagnostic purposes) * results in the death of the subject * results in the explant of the device
Time frame: 6 months
Population: This Safety Endpoint was prespecified as an aggregate analysis of all patients implanted with the device as well as patients where an implant was attempted. Results are not presented as an inter-arm comparison but rather against an objective performance criteria (OPC). This population includes 550 implanted patients + 25 patient attempts.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Freedom From a Device/System-related Complication (DSRC). | 567 cases |
Comparison: Analysis of DSRC was based on the following pre-specified objective performance criteria: the lower limit of the two-sided 95.2% confidence interval on the freedom from DSRC rate for all implantation cases was at least 80%. The statistical hypotheses were:~Null: (Freedom from device / system-related complications) ≤ 80%~Alternative: (Freedom from device / system-related complications) \> 80%p-value: <0.0001exact test of binomial proportions
Primary
Freedom From Pressure Sensor Failure
A pressure sensor failure occurs when the sensor malfunctions to the point that no readings can be obtained from it after all attempts are exhausted including troubleshooting the system to rule out any problems with the electronic components.
Time frame: 6 months
Population: This Safety Endpoint was prespecified as an aggregate analysis of all patients implanted with the device. Results are not presented as an inter-arm comparison but rather against an objective performance criteria (OPC).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Freedom From Pressure Sensor Failure | 550 participants |
Comparison: Analysis of sensor failures was based on the following pre-specified objective performance criteria: the lower limit of the two-sided 95.2% confidence interval on the freedom from pressure sensor failure rate for all patients implanted was at least 90%. The statistical hypotheses were:~Null: (Freedom from device / system-related complications) ≤ 90%~Alternative: (Freedom from device / system-related complications) \> 90%p-value: <0.0001exact test of binomial proportions
Primary
Rate of Heart Failure Related (HFR) Hospitalizations
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Rate of Heart Failure Related (HFR) Hospitalizations | 0.32 HFR hospitalizations/patient/6 months |
| Control | Rate of Heart Failure Related (HFR) Hospitalizations | 0.44 HFR hospitalizations/patient/6 months |
p-value: 0.0002Negative Binomial Regression
Secondary
Change From Baseline in Pulmonary Artery Mean Pressure
Change from baseline in pulmonary artery mean pressure was calculated using an area under the curve (AUC) methodology. All patients were instructed to take daily home readings for 180 days. By patient, a baseline average for the first 7 days of home readings was calculated. The difference between baseline and each daily reading was then determined and a corresponding daily AUC value was calculated. Finally, all daily AUC values were summed over the entire 180 day period resulting in a total AUC per patient. These data were aggregated for each randomization group and then compared. The unit of measure is mmHg x Days.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change From Baseline in Pulmonary Artery Mean Pressure | -155.7 mmHg * days | Standard Deviation 1088 |
| Control | Change From Baseline in Pulmonary Artery Mean Pressure | 33.1 mmHg * days | Standard Deviation 951.7 |
p-value: 0.0077ANCOVA
Secondary
Days Alive Outside of the Hospital
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Days Alive Outside of the Hospital | 174.4 days | Standard Deviation 31.1 |
| Control | Days Alive Outside of the Hospital | 172.1 days | Standard Deviation 37.8 |
p-value: 0.028Wilcoxon (Mann-Whitney)
Secondary
Proportion of Patients Hospitalized for Heart Failure
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Proportion of Patients Hospitalized for Heart Failure | 55 participants |
| Control | Proportion of Patients Hospitalized for Heart Failure | 80 participants |
p-value: 0.0292Fisher Exact
Secondary
Quality of Life - Minnesota Living With Heart Failure Questionnaire (MLHFQ)
THe MLHFQ is patient self-assessment of how heart failure affects his or her daily life. To measure the effects of symptoms, functional limitations, psychological distress on an individual's quality of life, the MLHFQ questionnaire asks each person to indicate using a 6-point, zero to five, Likert scale how much each of 21 facets prevented them from living as they desired. Total scores are provided as sums. The total score scale range is 0 - 105. A lower total score is indicative of better quality of life.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Quality of Life - Minnesota Living With Heart Failure Questionnaire (MLHFQ) | 45.2 units on a scale | Standard Deviation 26.4 |
| Control | Quality of Life - Minnesota Living With Heart Failure Questionnaire (MLHFQ) | 50.6 units on a scale | Standard Deviation 24.8 |
p-value: 0.0236t-test, 2 sided
Other Pre-specified
Freedom From a Device/System-related Complication (DSRC)
Time frame: Study duration: average patient follow-up of 15 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Freedom From a Device/System-related Complication (DSRC) | 498 participants |
Comparison: Analysis of DSRC was based on the following pre-specified objective performance criteria: the lower limit of the two-sided 95.2% confidence interval on the freedom from DSRC rate for all implanted patients was at least 80%. The statistical hypotheses were:~Null: (Freedom from device / system-related complications) ≤ 80%~Alternative: (Freedom from device / system-related complications) \> 80%p-value: <0.0001exact test of binomial proportions
Other Pre-specified
Freedom From Pressure Sensor Failure
Time frame: Study duration: average patient follow-up of 15 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Freedom From Pressure Sensor Failure | 498 participants |
Comparison: Analysis of sensor failures was based on the following pre-specified objective performance criteria: the lower limit of the two-sided 95.2% confidence interval on the freedom from pressure sensor failure rate for all implanted patients was at least 90%. The statistical hypotheses were:~Null: (Freedom from device / system-related complications) ≤ 90%~Alternative: (Freedom from device / system-related complications) \> 90%p-value: <0.0001exact test of binomial proportions
Other Pre-specified
Rate of HFR Hospitalizations
Time frame: Study duration: average patient follow-up of 15 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Rate of HFR Hospitalizations | 0.46 HFR hospitalizations/patient-year |
| Control | Rate of HFR Hospitalizations | 0.73 HFR hospitalizations/patient-year |
p-value: <0.0001Negative Binomial Regression