Acute Heart Failure, Decompensated Heart Failure, Heart Failure
Conditions
Keywords
Acute Heart failure, Hemodynamics, Pharmacokinetics, Renal Function
Brief summary
A randomized, double-blinded, placebo-controlled study of continuous 6-hour IV infusions of CXL-1427 in hospitalized patients with systolic heart failure.
Detailed description
This is a dose finding, randomized, double-blinded, placebo-controlled study of continuous 6-hour IV infusions of CXL-1427 in hospitalized patients with systolic heart failure which will first evaluate up to four ascending dose levels of CXL-1427 in up to four cohorts of 8 patients each (the Dose Escalation cohorts). Subsequently, up to three of the initial dose levels of CXL-1427 may be assessed in the additional Expansion cohorts of up to approximately 16 patients to gain further confidence in the results at these dose levels. The CXL-1427 dose that will be evaluated in the first cohort will be 3µg/kg/min. The dose levels for the next three sequential Dose Escalation cohorts will be dependent on clinical safety and tolerability, as well as the results of the invasive hemodynamic measurements.
Interventions
DRUGCXL-1427
DRUGPlacebo
Sponsors
Cardioxyl Pharmaceuticals, Inc
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion Criteria -In order to be eligible for study participation, a patient MUST: * Be ≥ 18 and ≤ 85 years of age; * Have a left ventricular ejection fraction (LVEF) ≤40%, as assessed by echocardiography, a multigated acquisition (MUGA) scan or magnetic resonance imaging (MRI) within 3 months prior to or during the current hospitalization; * Be hospitalized with a primary heart failure or heart failure-related reason, e.g., acute decompensation of heart failure, transplant evaluation, hemodynamic optimization prior to ambulatory inotropes or left ventricular assist device placement; * Have an indwelling pulmonary artery (PA) catheter in place for assessment of central hemodynamic parameters; \[Note: The indwelling catheter may already be in place for medically-indicated reasons, OR be placed for the primary purpose of monitoring the hemodynamic effects of the study drug. If the pulmonary artery catheter is to be placed for the sole purpose of monitoring the hemodynamic effect of the study drug, the patient must have a cardiac index (CI) ≤ 2.2L/min•m2 as measured by a non-invasive cardiac output monitor (NICaS device) ≤6 hours prior to placement of the catheter. In this setting,
Exclusion criteria
3 below also applies.\] * Have a Fick and/or thermodilution determination of cardiac index ≤2.5L/min•m2 at screening, i.e., ≤4 hours before the intended start of the study drug infusion; \[Note: For determinations of CI using the thermodilution method, a mean of three consecutive values measured approximately 5 minutes apart, none of which differs from the mean value by more than 15%, should be used.\] * Have a screening and baseline PCWP (or PAD, if a PCWP waveform cannot be reliably obtained) of ≥20 mmHg if systolic blood pressure is ≥100mmHg OR ≥22mmHg if systolic blood pressure is between 95-99mmHg (inclusive); * Be considered sufficiently stable to be expected not to require administration of any IV or oral vasoactive medications, including diuretics, for at least \ 10 hours, i.e., from 4 hours before performing baseline hemodynamic assessments until after the completion of the 6-hour study drug infusion; * Have a body weight of at least 50kg (110 pounds), but not more than 125kg (275 pounds), and have a body mass index (BMI) \<40kg/m2; * Have adequate peripheral forearm vein access or an available central line port for administration of study drug; * Be capable of understanding the nature of the trial; be willing and able to comply with the inpatient and outpatient study protocol requirements for the duration of the study (screening period, treatment period, and 30-day post-infusion follow-up period); and be willing to participate in the study, as documented by written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events | 30 days following the initiation of treatment | A treatment-emergent adverse event (TEAE) was defined as an AE with onset after the start of the study drug infusion at Hour 00:00 through 30 days after the stop of the study drug infusion. All TEAEs and pertinent subsets of TEAEs (e.g., TEAEs with onset during the infusion of study drug, serious TEAEs, etc.) were summarized by system organ class (SOC), preferred term (PT) and treatment group |
| Mean Time Averaged Change From Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion | Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion | The effect of CXL-1427 on PCWP is presented as the mean time-averaged change from baseline over the course of infusion of CXL-1427 or placebo in adjudicated pulmonary capillary wedge pressure (PCWP) on a modified intent-to-treat population |
| Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Diastolic Pressure (PAD) During the Infusion | Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation | Pulmonary artery diastolic pressure (PAD) was measured by an indwelling PA catheter. Pulmonary artery diastolic pressure (PAD) approximates pulmonary capillary wedge pressure in normal individuals. The effects of CXL-1427 on time-averaged PAD during the course of the infusion are presented. |
| Mean Time-Averaged Percent Change From Baseline in Cardiac Index (Fick) | Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation | Cardiac index is a measure of cardiac function, relating the cardiac output from the left ventricle in one minute to body surface area. It is calculated using the Fick principle, using oxygen consumption measured with a metabolic cart, hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation measured by co-oximetry. Cardiac index as calculated by the Fick method was performed using an assumed oxygen consumption value of 125 ml/min per m2 of body surface area. i.e., an assumed Fick method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Time-Averaged Change From Baseline in Diastolic Blood Pressure (DBP) During the Infusion | Baseline, Hour 24 after infusion, Follow-up visit 1 | Mean Time-Averaged Change from Baseline in Diastolic Blood Pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented |
| Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Systolic Pressure (PAS) During the Infusion | Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation | Pulmonary artery systolic pressure (PAS) was measured by an indwelling PA catheter. The effects of CXL-1427 on time-averaged PAS during the course of the infusion are presented |
| Mean Time-Averaged Change From Baseline in Heart Rate (HR) During the Infusion | Baseline, Hour 24 after infusion, Follow-up visit 1 | Mean Time-Averaged Change from Baseline in Heart Rate during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented |
| Mean Time-Averaged Change From Baseline in Adjudicated Right Atrial Pressure (RAP) During the Infusion | Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation | The effects of CXL-1427 on time-averaged RAP during the course of the infusion are presented |
| Mean Time-Averaged Change From Baseline in Mean Arterial Blood Pressure (MAP) During the Infusion | Baseline, Hour 24 after infusion, Follow-up visit 1 | Mean arterial pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented |
| Mean Time-Averaged Change From Baseline in Systolic Blood Pressure (SBP) During the Infusion | Baseline, Hour 24 after infusion, Follow-up visit 1 | Mean Time-Averaged Change from Baseline in Systolic Blood Pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented |
Countries
Germany, Jordan, Poland, Russia, United States
Participant flow
Pre-assignment details
A total of 70 participants were enrolled of which only 46 participants received treatment. 24 were not treated due to screen failures, 3 of the 24 were randomized but not dosed due to other reasons.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects received matching placebo intravenous (IV) infusion. | 12 |
| CXL-1427 3μg/kg/Min Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours. | 6 |
| CXL-1427 5μg/kg/Min Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours. | 9 |
| CXL-1427 7μg/kg/Min Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours. | 12 |
| CXL-1427 12μg/kg/Min Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours. | 7 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | CXL-1427 3μg/kg/Min | CXL-1427 5μg/kg/Min | CXL-1427 7μg/kg/Min | CXL-1427 12μg/kg/Min | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 62.7 years STANDARD_DEVIATION 9.25 | 63.5 years STANDARD_DEVIATION 3.51 | 61.1 years STANDARD_DEVIATION 11.36 | 61.6 years STANDARD_DEVIATION 10.26 | 48.3 years STANDARD_DEVIATION 17.49 | 60.0 years STANDARD_DEVIATION 11.1 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 10 Participants | 4 Participants | 8 Participants | 12 Participants | 5 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 1 / 6 | 0 / 9 | 0 / 12 | 0 / 7 |
| other Total, other adverse events | 3 / 12 | 6 / 6 | 6 / 9 | 7 / 12 | 4 / 7 |
| serious Total, serious adverse events | 1 / 12 | 3 / 6 | 1 / 9 | 3 / 12 | 1 / 7 |
Outcome results
Primary
Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Diastolic Pressure (PAD) During the Infusion
Pulmonary artery diastolic pressure (PAD) was measured by an indwelling PA catheter. Pulmonary artery diastolic pressure (PAD) approximates pulmonary capillary wedge pressure in normal individuals. The effects of CXL-1427 on time-averaged PAD during the course of the infusion are presented.
Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
Population: Modified Intent-To-Treat Analysis Set: all randomized patients who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Diastolic Pressure (PAD) During the Infusion | -0.21 mm Hg | Standard Deviation 3.35 |
| CXL-1427 3μg/kg/Min | Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Diastolic Pressure (PAD) During the Infusion | -3.69 mm Hg | Standard Deviation 2.55 |
| CXL-1427 5μg/kg/Min | Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Diastolic Pressure (PAD) During the Infusion | -4.17 mm Hg | Standard Deviation 4.02 |
| CXL-1427 7μg/kg/Min | Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Diastolic Pressure (PAD) During the Infusion | -2.67 mm Hg | Standard Deviation 3.63 |
| CXL-1427 12μg/kg/Min | Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Diastolic Pressure (PAD) During the Infusion | -3.17 mm Hg | Standard Deviation 1.82 |
p-value: =0.0076Mixed Models Analysis
p-value: =0.0052Mixed Models Analysis
p-value: =0.1064Mixed Models Analysis
p-value: =0.1151Mixed Models Analysis
Primary
Mean Time Averaged Change From Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion
The effect of CXL-1427 on PCWP is presented as the mean time-averaged change from baseline over the course of infusion of CXL-1427 or placebo in adjudicated pulmonary capillary wedge pressure (PCWP) on a modified intent-to-treat population
Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion
Population: Modified Intent-To-Treat Analysis Set: all randomized participants who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Time Averaged Change From Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion | -0.17 mm Hg | Standard Deviation 2.35 |
| CXL-1427 3μg/kg/Min | Mean Time Averaged Change From Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion | -3.00 mm Hg | Standard Deviation 3.06 |
| CXL-1427 5μg/kg/Min | Mean Time Averaged Change From Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion | -5.06 mm Hg | Standard Deviation 3.93 |
| CXL-1427 7μg/kg/Min | Mean Time Averaged Change From Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion | -4.42 mm Hg | Standard Deviation 4 |
| CXL-1427 12μg/kg/Min | Mean Time Averaged Change From Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion | -4.75 mm Hg | Standard Deviation 3.5 |
p-value: =0.0059Mixed Models Analysis
p-value: =0.0001Mixed Models Analysis
p-value: =0.0062Mixed Models Analysis
p-value: =0.0086Mixed Models Analysis
Primary
Mean Time-Averaged Percent Change From Baseline in Cardiac Index (Fick)
Cardiac index is a measure of cardiac function, relating the cardiac output from the left ventricle in one minute to body surface area. It is calculated using the Fick principle, using oxygen consumption measured with a metabolic cart, hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation measured by co-oximetry. Cardiac index as calculated by the Fick method was performed using an assumed oxygen consumption value of 125 ml/min per m2 of body surface area. i.e., an assumed Fick method.
Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
Population: Modified Intent-To-Treat Analysis Set: all randomized participants who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Time-Averaged Percent Change From Baseline in Cardiac Index (Fick) | 7.95 Percentage of change | Standard Deviation 16.15 |
| CXL-1427 3μg/kg/Min | Mean Time-Averaged Percent Change From Baseline in Cardiac Index (Fick) | 0.53 Percentage of change | Standard Deviation 18.12 |
| CXL-1427 5μg/kg/Min | Mean Time-Averaged Percent Change From Baseline in Cardiac Index (Fick) | 13.41 Percentage of change | Standard Deviation 23.53 |
| CXL-1427 7μg/kg/Min | Mean Time-Averaged Percent Change From Baseline in Cardiac Index (Fick) | 9.59 Percentage of change | Standard Deviation 11.91 |
| CXL-1427 12μg/kg/Min | Mean Time-Averaged Percent Change From Baseline in Cardiac Index (Fick) | -9.58 Percentage of change | Standard Deviation 18.02 |
p-value: =0.4241Mixed Models Analysis
p-value: =0.4035Mixed Models Analysis
p-value: =0.8308Mixed Models Analysis
p-value: =0.118Mixed Models Analysis
Primary
Number of Participants With Treatment-Emergent Adverse Events
A treatment-emergent adverse event (TEAE) was defined as an AE with onset after the start of the study drug infusion at Hour 00:00 through 30 days after the stop of the study drug infusion. All TEAEs and pertinent subsets of TEAEs (e.g., TEAEs with onset during the infusion of study drug, serious TEAEs, etc.) were summarized by system organ class (SOC), preferred term (PT) and treatment group
Time frame: 30 days following the initiation of treatment
Population: The safety analysis set consists of all randomized participants who received all or part of the infusion of the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | At least one Fatal TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | At least one Severe TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE leading to drug discontinuation | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related severe TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE | 3 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | At least one Serious TEAE | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related serious TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related fatal TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE leading to drug interruption | 0 Participants |
| CXL-1427 3μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Severe TEAE | 4 Participants |
| CXL-1427 3μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE leading to drug interruption | 0 Participants |
| CXL-1427 3μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related severe TEAE | 0 Participants |
| CXL-1427 3μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related fatal TEAE | 0 Participants |
| CXL-1427 3μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Serious TEAE | 3 Participants |
| CXL-1427 3μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related serious TEAE | 0 Participants |
| CXL-1427 3μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Fatal TEAE | 1 Participants |
| CXL-1427 3μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE leading to drug discontinuation | 0 Participants |
| CXL-1427 3μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE | 5 Participants |
| CXL-1427 5μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Fatal TEAE | 0 Participants |
| CXL-1427 5μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Serious TEAE | 1 Participants |
| CXL-1427 5μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE | 5 Participants |
| CXL-1427 5μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related fatal TEAE | 0 Participants |
| CXL-1427 5μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related serious TEAE | 0 Participants |
| CXL-1427 5μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE leading to drug discontinuation | 0 Participants |
| CXL-1427 5μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Severe TEAE | 0 Participants |
| CXL-1427 5μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE leading to drug interruption | 0 Participants |
| CXL-1427 5μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related severe TEAE | 0 Participants |
| CXL-1427 7μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE leading to drug interruption | 0 Participants |
| CXL-1427 7μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Fatal TEAE | 0 Participants |
| CXL-1427 7μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related fatal TEAE | 0 Participants |
| CXL-1427 7μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Serious TEAE | 3 Participants |
| CXL-1427 7μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Severe TEAE | 2 Participants |
| CXL-1427 7μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related severe TEAE | 0 Participants |
| CXL-1427 7μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE leading to drug discontinuation | 0 Participants |
| CXL-1427 7μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE | 7 Participants |
| CXL-1427 7μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related serious TEAE | 0 Participants |
| CXL-1427 12μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE leading to drug discontinuation | 1 Participants |
| CXL-1427 12μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related serious TEAE | 0 Participants |
| CXL-1427 12μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE | 3 Participants |
| CXL-1427 12μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Severe TEAE | 1 Participants |
| CXL-1427 12μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related severe TEAE | 0 Participants |
| CXL-1427 12μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Serious TEAE | 1 Participants |
| CXL-1427 12μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Fatal TEAE | 0 Participants |
| CXL-1427 12μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one Drug-related fatal TEAE | 0 Participants |
| CXL-1427 12μg/kg/Min | Number of Participants With Treatment-Emergent Adverse Events | At least one TEAE leading to drug interruption | 0 Participants |
Secondary
Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Systolic Pressure (PAS) During the Infusion
Pulmonary artery systolic pressure (PAS) was measured by an indwelling PA catheter. The effects of CXL-1427 on time-averaged PAS during the course of the infusion are presented
Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
Population: Modified Intent-To-Treat Analysis Set: all randomized participants who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Systolic Pressure (PAS) During the Infusion | -0.73 mm Hg | Standard Deviation 3.73 |
| CXL-1427 3μg/kg/Min | Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Systolic Pressure (PAS) During the Infusion | -6.42 mm Hg | Standard Deviation 2.59 |
| CXL-1427 5μg/kg/Min | Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Systolic Pressure (PAS) During the Infusion | -5.98 mm Hg | Standard Deviation 5.31 |
| CXL-1427 7μg/kg/Min | Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Systolic Pressure (PAS) During the Infusion | -6.26 mm Hg | Standard Deviation 5.09 |
| CXL-1427 12μg/kg/Min | Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Systolic Pressure (PAS) During the Infusion | -4.24 mm Hg | Standard Deviation 5.24 |
p-value: =0.0048Mixed Models Analysis
p-value: =0.0022Mixed Models Analysis
p-value: =0.0045Mixed Models Analysis
p-value: =0.0294Mixed Models Analysis
Secondary
Mean Time-Averaged Change From Baseline in Adjudicated Right Atrial Pressure (RAP) During the Infusion
The effects of CXL-1427 on time-averaged RAP during the course of the infusion are presented
Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
Population: Modified Intent-To-Treat Analysis Set: all randomized participants who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Time-Averaged Change From Baseline in Adjudicated Right Atrial Pressure (RAP) During the Infusion | -0.03 mm Hg | Standard Deviation 2.61 |
| CXL-1427 3μg/kg/Min | Mean Time-Averaged Change From Baseline in Adjudicated Right Atrial Pressure (RAP) During the Infusion | -1.92 mm Hg | Standard Deviation 2.91 |
| CXL-1427 5μg/kg/Min | Mean Time-Averaged Change From Baseline in Adjudicated Right Atrial Pressure (RAP) During the Infusion | -2.08 mm Hg | Standard Deviation 3.1 |
| CXL-1427 7μg/kg/Min | Mean Time-Averaged Change From Baseline in Adjudicated Right Atrial Pressure (RAP) During the Infusion | -2.17 mm Hg | Standard Deviation 2.42 |
| CXL-1427 12μg/kg/Min | Mean Time-Averaged Change From Baseline in Adjudicated Right Atrial Pressure (RAP) During the Infusion | -4.60 mm Hg | Standard Deviation 3.23 |
p-value: =0.2022Mixed Models Analysis
p-value: =0.0658Mixed Models Analysis
p-value: =0.0741Mixed Models Analysis
p-value: =0.0497Mixed Models Analysis
Secondary
Mean Time-Averaged Change From Baseline in Diastolic Blood Pressure (DBP) During the Infusion
Mean Time-Averaged Change from Baseline in Diastolic Blood Pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented
Time frame: Baseline, Hour 24 after infusion, Follow-up visit 1
Population: Modified Intent-To-Treat Analysis Set: all randomized participants who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Time-Averaged Change From Baseline in Diastolic Blood Pressure (DBP) During the Infusion | -0.09 mm Hg | Standard Deviation 8.3 |
| CXL-1427 3μg/kg/Min | Mean Time-Averaged Change From Baseline in Diastolic Blood Pressure (DBP) During the Infusion | -4.42 mm Hg | Standard Deviation 5.22 |
| CXL-1427 5μg/kg/Min | Mean Time-Averaged Change From Baseline in Diastolic Blood Pressure (DBP) During the Infusion | -5.93 mm Hg | Standard Deviation 11.07 |
| CXL-1427 7μg/kg/Min | Mean Time-Averaged Change From Baseline in Diastolic Blood Pressure (DBP) During the Infusion | -7.33 mm Hg | Standard Deviation 8.51 |
| CXL-1427 12μg/kg/Min | Mean Time-Averaged Change From Baseline in Diastolic Blood Pressure (DBP) During the Infusion | -7.71 mm Hg | Standard Deviation 8.03 |
p-value: =0.1391Mixed Models Analysis
p-value: =0.1724Mixed Models Analysis
p-value: =0.1245Mixed Models Analysis
p-value: =0.169Mixed Models Analysis
Secondary
Mean Time-Averaged Change From Baseline in Heart Rate (HR) During the Infusion
Mean Time-Averaged Change from Baseline in Heart Rate during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented
Time frame: Baseline, Hour 24 after infusion, Follow-up visit 1
Population: Modified Intent-To-Treat Analysis Set: all randomized participants who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Time-Averaged Change From Baseline in Heart Rate (HR) During the Infusion | -0.79 Beats/min | Standard Deviation 6.34 |
| CXL-1427 3μg/kg/Min | Mean Time-Averaged Change From Baseline in Heart Rate (HR) During the Infusion | 1.06 Beats/min | Standard Deviation 3.74 |
| CXL-1427 5μg/kg/Min | Mean Time-Averaged Change From Baseline in Heart Rate (HR) During the Infusion | -3.09 Beats/min | Standard Deviation 6.84 |
| CXL-1427 7μg/kg/Min | Mean Time-Averaged Change From Baseline in Heart Rate (HR) During the Infusion | 1.00 Beats/min | Standard Deviation 7.08 |
| CXL-1427 12μg/kg/Min | Mean Time-Averaged Change From Baseline in Heart Rate (HR) During the Infusion | -4.52 Beats/min | Standard Deviation 16.92 |
p-value: =0.2789Mixed Models Analysis
p-value: =0.91Mixed Models Analysis
p-value: =0.4936Mixed Models Analysis
p-value: =0.992Mixed Models Analysis
Secondary
Mean Time-Averaged Change From Baseline in Mean Arterial Blood Pressure (MAP) During the Infusion
Mean arterial pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented
Time frame: Baseline, Hour 24 after infusion, Follow-up visit 1
Population: Modified Intent-To-Treat Analysis Set: all randomized participants who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Time-Averaged Change From Baseline in Mean Arterial Blood Pressure (MAP) During the Infusion | -1.11 mm Hg | Standard Deviation 5.01 |
| CXL-1427 3μg/kg/Min | Mean Time-Averaged Change From Baseline in Mean Arterial Blood Pressure (MAP) During the Infusion | -5.84 mm Hg | Standard Deviation 4.46 |
| CXL-1427 5μg/kg/Min | Mean Time-Averaged Change From Baseline in Mean Arterial Blood Pressure (MAP) During the Infusion | -4.75 mm Hg | Standard Deviation 10.93 |
| CXL-1427 7μg/kg/Min | Mean Time-Averaged Change From Baseline in Mean Arterial Blood Pressure (MAP) During the Infusion | -7.16 mm Hg | Standard Deviation 7.67 |
| CXL-1427 12μg/kg/Min | Mean Time-Averaged Change From Baseline in Mean Arterial Blood Pressure (MAP) During the Infusion | -6.69 mm Hg | Standard Deviation 5.67 |
p-value: =0.1842Mixed Models Analysis
p-value: =0.3328Mixed Models Analysis
p-value: =0.1465Mixed Models Analysis
p-value: =0.2799Mixed Models Analysis
Secondary
Mean Time-Averaged Change From Baseline in Systolic Blood Pressure (SBP) During the Infusion
Mean Time-Averaged Change from Baseline in Systolic Blood Pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented
Time frame: Baseline, Hour 24 after infusion, Follow-up visit 1
Population: Modified Intent-To-Treat Analysis Set: all randomized participants who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Time-Averaged Change From Baseline in Systolic Blood Pressure (SBP) During the Infusion | -3.15 mm Hg | Standard Deviation 5.53 |
| CXL-1427 3μg/kg/Min | Mean Time-Averaged Change From Baseline in Systolic Blood Pressure (SBP) During the Infusion | -8.69 mm Hg | Standard Deviation 4.43 |
| CXL-1427 5μg/kg/Min | Mean Time-Averaged Change From Baseline in Systolic Blood Pressure (SBP) During the Infusion | -2.41 mm Hg | Standard Deviation 12.57 |
| CXL-1427 7μg/kg/Min | Mean Time-Averaged Change From Baseline in Systolic Blood Pressure (SBP) During the Infusion | -6.81 mm Hg | Standard Deviation 9.54 |
| CXL-1427 12μg/kg/Min | Mean Time-Averaged Change From Baseline in Systolic Blood Pressure (SBP) During the Infusion | -4.64 mm Hg | Standard Deviation 4.04 |
p-value: =0.2499Mixed Models Analysis
p-value: =0.8281Mixed Models Analysis
p-value: =0.4121Mixed Models Analysis
p-value: =0.8592Mixed Models Analysis