Pulmonary Hypertension
Conditions
Brief summary
mTOR activation has been shown to be relevant in the development and progression of pulmonary hypertension. Inhibition of mTOR has been shown to reverse or regress pulmonary hypertension in animal models. nab-Sirolimus (also known as ABI-009, nab-rapamycin) is an albumin-bound mTOR inhibitor with improved penetration in lung tissue.
Detailed description
nab-Sirolimus, an mTOR inhibitor, is a novel formulation of albumin-bound sirolimus nanoparticles and has produced encouraging results in oncology at doses up to 100 mg/m2 given once weekly IV. This study is aimed to determine the optimal clinial dose of once weekly IV nab-sirolimus in patients with PAH and safety of 16 weeks of therapy (Phase 1, Dose finding Safety Part) followed optionally by up to 32 weeks of therapy (Extension Part).
Interventions
DRUGnab-sirolimus
nab-sirolimus is an mTOR inhibitor
Sponsors
Aadi Bioscience, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female age \>18 years old with a current diagnosis of WHO Group 1 PAH including idiopathic pulmonary arterial hypertension (IPAH), heritable pulmonary arterial hypertension (HPAH), drug and toxin induced PAH, or PAH associated with connective tissue disease, or congenital heart defects (repaired greater than 1 year prior to Screening) * Must meet following hemodynamic definition prior to initiation of study drug * Mean PAP of ≥ 25 mm Hg * PCWP or left ventricular end diastolic pressure (LVEDP) of ≤ 15 mm * PVR \> 5 mmHg/L/min (Woods unit) * Functional class II or III according to the WHO set forth at the Dana Point Classification 2008 Meeting * On 2 or more specific standard PAH therapies (for ≥ 8 consecutive weeks and at stable dose for ≥ 4 consecutive weeks) unless documented inability to tolerate 2 standard therapies * Meet the following criteria determined by pulmonary function tests completed no more than 24 weeks prior to screening, performed with or without bronchodilation: * Forced expiratory volume in one second (FEV1) ≥ 55% of predicted normal * FEV1:forced vital capacity (FVC) ratio ≥ 0.60 * 6MWD ≥150 meters and ≤450 meters * Negative serum pregnancy test * Female of childbearing age either surgically sterilized or using acceptable method of contraception * Ability to provide written informed consent by the patient or legal guardian
Exclusion criteria
* History of heart disease including left ventricular ejection fraction (LVEF) ≤ 40% or clinically significant valvular constrictive or atherosclerotic heart disease (myocardial infarction, angina, cerebrovascular accident) * History of malignancy in 2 years prior to enrollment * Pulmonary hypertension (PH) belonging to groups 2 to 5 of the 2013 Nice classification * Current or recent (\< 3 months) use of inotropic or vasopressor agents for the treatment of PAH * Recent (\< 2 months) PAH related hospital admission * History of allergic reactions attributed to compounds of similar chemical or biologic composition including macrolide (eg, azithromycin, clarithromycin, dirithromycin, and erythromycin) and ketolide antibiotics * Uncontrolled diabetes mellitus as defined by HbA1c \>8% despite adequate therapy * Uncontrolled hyperlipidemia (serum triglyceride ≥300 mg/dL) * Serum cholesterol ≥350 mg/dL * Surgery within 3 months of start date of study drug * Baseline cytopenias: * Absolute Neutrophil Count ≤ 1.5 x 109/L * Hemoglobin ≤ 9 g/dL * Platelet count \< 100,000/mm3 * Baseline liver disease: ALT/AST, total bilirubin, alkaline phosphatase \>1.5 x ULN * Baseline renal disease: creatinine \>1.5 ULN and/or creatinine clearance (Cockcroft formula) ≤ 30 mL/min * Inability to attend scheduled clinic visits * Prior use of study drug within previous 6 months from enrollment * Previous lung transplant * Naïve to available standard PAH therapy * Concomitant genetic or acquired immunosuppressive diseases (such as HIV, AIDS) * Uncontrolled intercurrent illness that in the opinion of the investigator would limit compliance and tolerance to study requirements (eg, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, uncontrolled hypertension, coronary artery disease, or psychiatric illness/social situations) * Concomitant enrollment in another investigational treatment protocol for PAH * Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the first dose of ABI-009. Additionally, use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfanide) within the 14 days prior to receiving the first dose of ABI-009
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting Toxicities | 16 weeks | A dose-limiting toxicity (DLT) was defined as a study drug-related Grade ≥3 hematologic AE or persistent intolerable nonhematologic AE of any grade that occurred during the first 4 weeks of treatment, requiring dose reduction or permanent discontinuation of the study drug, in the opinion of the Investigator. The number and percent of patients with a DLT were to be reported by dose cohorts in the Phase 1 dose finding part of the study if any were observed in the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | 17 Weeks | Median Percent Change from Baseline to Week 17 (after 16 weeks of treatment) in RHC based on Central Lab Analysis (Pulmonary vascular resistance, Cardiac Output, Cardiac Index, Stroke Volume) |
| 6-minute Walk Distance (6MWD) | 17 Weeks | Median Percent Change from Baseline to Week 17 (after 16 weeks of treatment) in 6MWD |
| N-terminal Pro-brain Natriuretic Peptide (NT Pro-BNP) | 17 Weeks | Median Percent Change from Baseline to Week 17 (after 16 weeks of treatment) in NT Pro-BNP |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nab-Sirolimus Dose Cohort 1 nab-Sirolimus Dose Cohort 1 at 10 mg/m\^2, given once weekly intravenously for 16 weeks. | 4 |
| Nab-Sirolimus Dose Cohort 2 nab-Sirolimus Dose Cohort 2 at 1.0 mg/m\^2, given once weekly intravenously for 16 weeks. | 3 |
| Nab-Sirolimus Dose Cohort 3 nab-Sirolimus Dose Cohort 3 at 2.5 mg/m\^2, given once weekly intravenously for 16 weeks. | 4 |
| Nab-Sirolimus Dose Cohort 4 nab-Sirolimus Dose Cohort 4 at 5.0 mg/m\^2, given once weekly intravenously for 16 weeks. | 3 |
| Nab-Sirolimus Dose Cohort 5 nab-Sirolimus Dose Cohort 5 at 7.5 mg/m\^2, given once weekly intravenously for 16 weeks. | 1 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| 16-Week Dose-finding Safety Part | Adverse Event | 1 | 0 | 0 | 0 | 0 |
| 16-Week Dose-finding Safety Part | COVID-19 risk | 0 | 0 | 0 | 1 | 0 |
| 32-Week Optional Extension Part | Adverse Event | 0 | 0 | 1 | 0 | 0 |
| 32-Week Optional Extension Part | Lost to Follow-up | 0 | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Nab-Sirolimus Dose Cohort 1 | Nab-Sirolimus Dose Cohort 2 | Nab-Sirolimus Dose Cohort 3 | Nab-Sirolimus Dose Cohort 4 | Nab-Sirolimus Dose Cohort 5 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 56.5 years | 45 years | 38.5 years | 45 years | 28 years | 45 years |
| Body Surface Area 16-Week Dose-finding Safety Part | 2.1 m^2 | 1.6 m^2 | 1.6 m^2 | 1.8 m^2 | 1.8 m^2 | 1.7 m^2 |
| Body Surface Area 32-Week Optional Extension Part | — | 1.5 m^2 | 1.7 m^2 | 1.9 m^2 | 1.8 m^2 | 1.8 m^2 |
| Ethnicity (NIH/OMB) 16-Week Dose-finding Safety Part Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) 16-Week Dose-finding Safety Part Not Hispanic or Latino | 4 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 12 Participants |
| Ethnicity (NIH/OMB) 16-Week Dose-finding Safety Part Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) 32-Week Optional Extension Part Hispanic or Latino | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) 32-Week Optional Extension Part Not Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) 32-Week Optional Extension Part Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 16-Week Dose-finding Part American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) 16-Week Dose-finding Part Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 16-Week Dose-finding Part Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 16-Week Dose-finding Part More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 16-Week Dose-finding Part Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 16-Week Dose-finding Part Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 16-Week Dose-finding Part White | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 14 Participants |
| Race (NIH/OMB) 32-Week Optional Extension Part American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) 32-Week Optional Extension Part Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 32-Week Optional Extension Part Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 32-Week Optional Extension Part More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 32-Week Optional Extension Part Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 32-Week Optional Extension Part Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 32-Week Optional Extension Part White | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 6 Participants |
| Region of Enrollment United States | 4 participants | 3 participants | 4 participants | 3 participants | 1 participants | 15 participants |
| Sex: Female, Male 16-Week Dose-finding Safety Part Female | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 14 Participants |
| Sex: Female, Male 16-Week Dose-finding Safety Part Male | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male 32-Week Optional Extension Part Female | 0 Participants | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male 32-Week Optional Extension Part Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 | 0 / 4 | 0 / 3 | 0 / 1 | 0 / 15 | 0 / 1 | 0 / 4 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 4 / 4 | 3 / 3 | 1 / 1 | 15 / 15 | 0 / 1 | 4 / 4 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 1 / 4 | 0 / 3 | 0 / 4 | 1 / 3 | 0 / 1 | 2 / 15 | 0 / 1 | 1 / 4 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Dose-limiting Toxicities
A dose-limiting toxicity (DLT) was defined as a study drug-related Grade ≥3 hematologic AE or persistent intolerable nonhematologic AE of any grade that occurred during the first 4 weeks of treatment, requiring dose reduction or permanent discontinuation of the study drug, in the opinion of the Investigator. The number and percent of patients with a DLT were to be reported by dose cohorts in the Phase 1 dose finding part of the study if any were observed in the study.
Time frame: 16 weeks
Population: The Treated Population included all patients who received at least 1 dose of nab sirolimus. This population was used for analyses of safety.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nab-Sirolimus Dose Cohort 1 | Dose-limiting Toxicities | 0 Participants |
| Nab-Sirolimus Dose Cohort 2 | Dose-limiting Toxicities | 0 Participants |
| Nab-Sirolimus Dose Cohort 3 | Dose-limiting Toxicities | 0 Participants |
| Nab-Sirolimus Dose Cohort 4 | Dose-limiting Toxicities | 0 Participants |
| Nab-Sirolimus Dose Cohort 5 | Dose-limiting Toxicities | 0 Participants |
Secondary
6-minute Walk Distance (6MWD)
Median Percent Change from Baseline to Week 17 (after 16 weeks of treatment) in 6MWD
Time frame: 17 Weeks
Population: The Efficacy Evaluable Population included all patients who received at least 1 dose of nab-sirolimus and had at least one post-baseline efficacy assessment. This population was used for analyses of efficacy (N=13).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Sirolimus Dose Cohort 1 | 6-minute Walk Distance (6MWD) | -2.0 percentage of change |
| Nab-Sirolimus Dose Cohort 2 | 6-minute Walk Distance (6MWD) | 16.0 percentage of change |
| Nab-Sirolimus Dose Cohort 3 | 6-minute Walk Distance (6MWD) | 13.3 percentage of change |
| Nab-Sirolimus Dose Cohort 4 | 6-minute Walk Distance (6MWD) | 16.6 percentage of change |
| Nab-Sirolimus Dose Cohort 5 | 6-minute Walk Distance (6MWD) | 21.0 percentage of change |
| Overall | 6-minute Walk Distance (6MWD) | 15.0 percentage of change |
Secondary
N-terminal Pro-brain Natriuretic Peptide (NT Pro-BNP)
Median Percent Change from Baseline to Week 17 (after 16 weeks of treatment) in NT Pro-BNP
Time frame: 17 Weeks
Population: The Efficacy Evaluable Population included all patients who received at least 1 dose of nab-sirolimus and had at least one post-baseline efficacy assessment. This population was used for analyses of efficacy (N=12).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Sirolimus Dose Cohort 1 | N-terminal Pro-brain Natriuretic Peptide (NT Pro-BNP) | -49.0 percentage of change |
| Nab-Sirolimus Dose Cohort 2 | N-terminal Pro-brain Natriuretic Peptide (NT Pro-BNP) | -34.6 percentage of change |
| Nab-Sirolimus Dose Cohort 3 | N-terminal Pro-brain Natriuretic Peptide (NT Pro-BNP) | -7.1 percentage of change |
| Nab-Sirolimus Dose Cohort 4 | N-terminal Pro-brain Natriuretic Peptide (NT Pro-BNP) | -10.8 percentage of change |
| Nab-Sirolimus Dose Cohort 5 | N-terminal Pro-brain Natriuretic Peptide (NT Pro-BNP) | -17.0 percentage of change |
| Overall | N-terminal Pro-brain Natriuretic Peptide (NT Pro-BNP) | -19.3 percentage of change |
Secondary
Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume)
Median Percent Change from Baseline to Week 17 (after 16 weeks of treatment) in RHC based on Central Lab Analysis (Pulmonary vascular resistance, Cardiac Output, Cardiac Index, Stroke Volume)
Time frame: 17 Weeks
Population: The Efficacy Evaluable Population included all patients who received at least 1 dose of nab-sirolimus and had at least one post-baseline efficacy assessment. This population was used for analyses of efficacy (N=13).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nab-Sirolimus Dose Cohort 1 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Thermodilution Cardiac Output Mean (L/minute) | 40.1 percentage of change |
| Nab-Sirolimus Dose Cohort 1 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Stroke Volume (mL) | 11.6 percentage of change |
| Nab-Sirolimus Dose Cohort 1 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Cardiac Index (L/minute/m2) | 40.1 percentage of change |
| Nab-Sirolimus Dose Cohort 1 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Pulmonary Vascular Resistance (dyn×sec/cm5) | -30.1 percentage of change |
| Nab-Sirolimus Dose Cohort 2 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Thermodilution Cardiac Output Mean (L/minute) | -15.4 percentage of change |
| Nab-Sirolimus Dose Cohort 2 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Stroke Volume (mL) | -14.4 percentage of change |
| Nab-Sirolimus Dose Cohort 2 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Pulmonary Vascular Resistance (dyn×sec/cm5) | 10.9 percentage of change |
| Nab-Sirolimus Dose Cohort 2 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Cardiac Index (L/minute/m2) | -16.5 percentage of change |
| Nab-Sirolimus Dose Cohort 3 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Stroke Volume (mL) | 11.0 percentage of change |
| Nab-Sirolimus Dose Cohort 3 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Thermodilution Cardiac Output Mean (L/minute) | 10.8 percentage of change |
| Nab-Sirolimus Dose Cohort 3 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Cardiac Index (L/minute/m2) | 13.5 percentage of change |
| Nab-Sirolimus Dose Cohort 3 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Pulmonary Vascular Resistance (dyn×sec/cm5) | -3.5 percentage of change |
| Nab-Sirolimus Dose Cohort 4 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Cardiac Index (L/minute/m2) | 9.4 percentage of change |
| Nab-Sirolimus Dose Cohort 4 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Stroke Volume (mL) | 6.3 percentage of change |
| Nab-Sirolimus Dose Cohort 4 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Thermodilution Cardiac Output Mean (L/minute) | 9.6 percentage of change |
| Nab-Sirolimus Dose Cohort 4 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Pulmonary Vascular Resistance (dyn×sec/cm5) | -15.7 percentage of change |
| Nab-Sirolimus Dose Cohort 5 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Thermodilution Cardiac Output Mean (L/minute) | 27.4 percentage of change |
| Nab-Sirolimus Dose Cohort 5 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Stroke Volume (mL) | 10.5 percentage of change |
| Nab-Sirolimus Dose Cohort 5 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Cardiac Index (L/minute/m2) | 31.2 percentage of change |
| Nab-Sirolimus Dose Cohort 5 | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Pulmonary Vascular Resistance (dyn×sec/cm5) | -30.8 percentage of change |
| Overall | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Stroke Volume (mL) | 10.5 percentage of change |
| Overall | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Pulmonary Vascular Resistance (dyn×sec/cm5) | -20.5 percentage of change |
| Overall | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Thermodilution Cardiac Output Mean (L/minute) | 16.9 percentage of change |
| Overall | Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume) | Cardiac Index (L/minute/m2) | 21.4 percentage of change |