Targeting the Right Ventricle in Pulmonary Hypertension

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01839110
• Collaborator: The Cardiovascular Medical Research and Education Fund (Other), Brigham and Women's Hospital (Other), University of Maryland (Other), Yale University (Other), Washington University School of Medicine (Other)
• Enrollment: 22
• Locations: 3
• Arms: 3
• Actual Duration (Months): 54
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is looking to see if giving ranolazine to subjects on stable pulmonary hypertension specific therapies but with right ventricular dysfunction (RVEF <45%) would improve their outcome. This study is accompanied by a baseline comparison of the metabolic profiling/microRNA/iPS cells of subjects with and without right ventricular dysfunction.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Hypertension	Drug: Ranolazine; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo Controlled, Multi-center Study to Assess the Effect of Ranolazine on Outcomes in Subjects With Pulmonary Hypertension and Right Ventricular Dysfunction Accompanied by a Comparative Study of Cellular Metabolism in Subjects With Pulmonary Hypertension With and Without Right Ventricular Dysfunction
• Actual Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Jan 1, 2018
• Actual Study Completion Date: Jan 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ranolazine Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day	Drug: Ranolazine; Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day and continue for a total of 26 weeks.; Other Names: Ranexa
Placebo Comparator: Placebo Placebo by mouth twice per day	Drug: Placebo; Placebo by mouth twice per day for a total of 26 weeks.
No Intervention: Observational Patients with pulmonary hypertension who have normal RV function (RVEF >=45%) will undergo same procedures in the observational arm but will not receive an intervention.

Outcome Measures

Primary Outcome Measures

1. Changes in Right Ventricular Ejection Fraction [6 months]

   right ventricular ejection fraction by cardiac MRI

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Symptomatic pulmonary hypertension based on one of the following criteria: Idiopathic pulmonary arterial hypertension, Familial pulmonary arterial hypertension, pulmonary hypertension associated with connective tissue disease, chronic thromboembolic pulmonary hypertension-nonsurgical/distal vessel disease or patients who are reluctant to go to surgery within a 6-month period and are willing to participate, simple congenital such as repaired atrial septal defect or ventricular septal defect or unrepaired small atrial septal defect or ventricular septal defect with persistent and out of proportion pulmonary arterial hypertension, group 3 patients who have a component of pulmonary arterial hypertension, pulmonary arterial hypertension caused by conditions affect the veins and small vessels of the lungs, sickle cell disease, group 5 pulmonary hypertension such as polycythemia vera, essential thrombocythemia, sarcoidosis, or vasculitis, or metabolic disorder.

• WHO functional class II, III, or IV

• Mean pulmonary artery pressure >25 mmHg at rest

• Pulmonary capillary wedge pressure or left ventricular end diastolic pressure < 15 mmHg

• Baseline 6-minute walk test distance > 50 meters

• Stable on baseline existing PH specific therapy for 12 weeks with no dosage change within 28 days prior to screening.

Exclusion Criteria:

• Previous treatment with or prior sensitivity to ranolazine

• Any family history of corrected QT interval prolongation, congenital long QT syndrome, or receiving drugs that prolong the corrected QT interval

• Parenchymal lung disease showing total lung capacity < 50% of predicted OR forced expiratory volume at one second/forced vital capacity < 50%

• Portal hypertension associated with liver disease

• Left sided heart disease including any of the following: moderate or greater aortic or mitral valve disease, Any left ventricle cardiomyopathy, Left ventricular systolic dysfunction defined as an ejection fraction < 50%, Symptomatic coronary artery disease

• Uncontrolled hypertension

• Uncontrolled diabetes

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland	Baltimore	Maryland	United States	21201
2	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
3	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• The Cardiovascular Medical Research and Education Fund
• Brigham and Women's Hospital
• University of Maryland
• Yale University
• Washington University School of Medicine

Investigators

• Principal Investigator: Yuchi Han, MD, University of Pennsylvania

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 16, 2015

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01839110
• Other Study ID Numbers: 817785
• First Posted: Apr 24, 2013
• Last Update Posted: Feb 5, 2019
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by University of Pennsylvania: pulmonary hypertension; right ventricular function; ranolazine
• Additional relevant MeSH terms: Hypertension, Pulmonary; Hypertension; Ranolazine

Study Results

Participant Flow

Arm/Group Title	Ranolazine	Placebo	Observational
Arm/Group Description	Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day Ranolazine: Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day and continue for a total of 26 weeks.	Placebo by mouth twice per day Placebo: Placebo by mouth twice per day for a total of 26 weeks.	Patients with pulmonary hypertension who have normal RV function (RVEF >=45%) will undergo same procedures in the observational arm but will not receive an intervention.
Period Title: Overall Study
STARTED	7	6	9
COMPLETED	4	4	6
NOT COMPLETED	3	2	3

Baseline Characteristics

Arm/Group Title	Ranolazine	Placebo	Observational	Total
Arm/Group Description	Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day Ranolazine: Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day and continue for a total of 26 weeks.	Placebo by mouth twice per day Placebo: Placebo by mouth twice per day for a total of 26 weeks.	Patients with pulmonary hypertension who have normal RV function (RVEF >=45%) will undergo same procedures in the observational arm but will not receive an intervention.	Total of all reporting groups
Overall Participants	7	6	9	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.0 (19.7)	57.7 (6.8)	53.2 (17.9)	54.4 (15.9)
Sex: Female, Male (Count of Participants)
Female	3 42.9%	4 66.7%	6 66.7%	13 59.1%
Male	4 57.1%	2 33.3%	3 33.3%	9 40.9%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%	6 100%	9 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Changes in Right Ventricular Ejection Fraction
Description	right ventricular ejection fraction by cardiac MRI
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Completers

Arm/Group Title	Ranolazine	Placebo	Observational
Arm/Group Description	Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day Ranolazine: Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day and continue for a total of 26 weeks.	Placebo by mouth twice per day Placebo: Placebo by mouth twice per day for a total of 26 weeks.	Patients with pulmonary hypertension who have normal RV function (RVEF >=45%) will undergo same procedures in the observational arm but will not receive an intervention.
Measure Participants	4	3	6
Least Squares Mean (Standard Error) [percentage]	5.8 (2.0)	-4.7 (3.2)	0.49 (3.2)

Adverse Events

Time Frame	7 months. 6 months of trial and adverse events are gathered for 30 additional days
Arm/Group Title	Ranolazine		Placebo		Observational
Arm/Group Description	Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day Ranolazine: Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day and continue for a total of 26 weeks.		Placebo by mouth twice per day Placebo: Placebo by mouth twice per day for a total of 26 weeks.		Patients with pulmonary hypertension who have normal RV function (RVEF >=45%) will undergo same procedures in the observational arm but will not receive an intervention.
All Cause Mortality
	Ranolazine		Placebo		Observational
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/6 (0%)		0/9 (0%)
Serious Adverse Events
	Ranolazine		Placebo		Observational
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		1/6 (16.7%)		0/9 (0%)
Cardiac disorders
heart failure hospitalization	1/7 (14.3%)	1	1/6 (16.7%)	1	0/9 (0%)	0
Other (Not Including Serious) Adverse Events
	Ranolazine		Placebo		Observational
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/7 (71.4%)		2/6 (33.3%)		2/6 (33.3%)
Cardiac disorders
chest pain	0/7 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Gastrointestinal disorders
nausea	2/7 (28.6%)	2	0/6 (0%)	0	1/6 (16.7%)	1
General disorders
fatigue	1/7 (14.3%)	1	0/6 (0%)	0	0/6 (0%)	0
face edema	1/7 (14.3%)	1	0/6 (0%)	0	0/6 (0%)	0
Renal and urinary disorders
hyponatremia	1/7 (14.3%)	1	0/6 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
hemoptysis	0/7 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Skin and subcutaneous tissue disorders
hair loss	0/7 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.