Targeting Right Ventricle in Pulmonary Hypertension Gilead

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT02829034
• Collaborator: Brigham and Women's Hospital (Other), University of Maryland (Other), Gilead Sciences (Industry)
• Enrollment: 22
• Locations: 3
• Arms: 2
• Actual Duration (Months): 18
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study is looking to see if giving ranolazine to subjects on stable pulmonary hypertension therapies but with right ventricular dysfunction (RVEF <45%) will improve their health by improving right ventricular (RV) function.

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 in Subjects With Pulmonary Hypertension and Right Ventricular Dysfunction Using Cardiovascular MRI
• Actual Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Jan 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ranolazine Ranolazine 500mg by mouth twice per day and after two weeks increase to 1000mg by mouth twice per day	Drug: Ranolazine; Ranolazine 500mg by mouth twice per day and after two weeks increases 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

Outcome Measures

Primary Outcome Measures

1. Absolute Change From Baseline Right Ventricular Ejection Fraction (the Unit is Percentage) [26 weeks]

   Change in right ventricle ejection fraction as assessed by MRI

Secondary Outcome Measures

1. Percent Change in 6min-walk-test Distance [6 months]

   6-minute walk test

2. Change in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) [6 months]

   NT-proBNP measured at 6-months compared to baseline

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 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

• Vasculitis

• Metabolic disorder

• World Health Organization 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

• Pulmonary vascular resistance > 3 mmHg/L/min

• Right ventricle ejection fraction < 45%

• 6-minute walk test distance > 50 meters

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 chronic 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 systemic hypertension

• Implantable cardioverter-defibrillator, Pacemaker, hazardous metallic implants or any other contraindication to MRI.

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
• Brigham and Women's Hospital
• University of Maryland
• Gilead Sciences

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 9, 2016

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT02829034
• Other Study ID Numbers: 824808
• First Posted: Jul 12, 2016
• Last Update Posted: Feb 26, 2019
• Last Verified: Feb 1, 2019

• 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
Arm/Group Description	Ranolazine 500mg by mouth twice per day and after two weeks increase to 1000mg by mouth twice per day Ranolazine: Ranolazine 500mg by mouth twice per day and after two weeks increases 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
Period Title: Overall Study
STARTED	14	8
COMPLETED	9	6
NOT COMPLETED	5	2

Baseline Characteristics

Arm/Group Title	Ranolazine	Placebo	Total
Arm/Group Description	Ranolazine 500mg by mouth twice per day and after two weeks increase to 1000mg by mouth twice per day Ranolazine: Ranolazine 500mg by mouth twice per day and after two weeks increases 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	Total of all reporting groups
Overall Participants	14	8	22
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 92.9%	7 87.5%	20 90.9%
>=65 years	1 7.1%	1 12.5%	2 9.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.4 (16.9)	53.6 (14.1)	54.8 (16.0)
Sex: Female, Male (Count of Participants)
Female	8 57.1%	5 62.5%	13 59.1%
Male	6 42.9%	3 37.5%	9 40.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 35.7%	2 25%	7 31.8%
White	9 64.3%	6 75%	15 68.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	14 100%	8 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Absolute Change From Baseline Right Ventricular Ejection Fraction (the Unit is Percentage)
Description	Change in right ventricle ejection fraction as assessed by MRI
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

participants who completed follow up study at 6 months.

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Ranolazine 500mg by mouth twice per day and after two weeks increase to 1000mg by mouth twice per day Ranolazine: Ranolazine 500mg by mouth twice per day and after two weeks increases 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
Measure Participants	9	6
Least Squares Mean (Standard Error) [percentage]	7.56 (1.72)	-3.99 (2.23)

2. Secondary Outcome

Title	Percent Change in 6min-walk-test Distance
Description	6-minute walk test
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

complete and recorded data

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Ranolazine 500mg by mouth twice per day and after two weeks increase to 1000mg by mouth twice per day Ranolazine: Ranolazine 500mg by mouth twice per day and after two weeks increases 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
Measure Participants	8	5
Least Squares Mean (Standard Error) [percentage of distance walked]	-0.09 (0.095)	-0.06 (0.125)

3. Secondary Outcome

Title	Change in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
Description	NT-proBNP measured at 6-months compared to baseline
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

completers

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	Ranolazine 500mg by mouth twice per day and after two weeks increase to 1000mg by mouth twice per day Ranolazine: Ranolazine 500mg by mouth twice per day and after two weeks increases 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
Measure Participants	9	6
Least Squares Mean (Standard Error) [pg/mL]	-119.72 (276.42)	-287.75 (353.81)

Adverse Events

Time Frame	7 months including 6 months of drug treatment and 1 month post treatment
Arm/Group Title	Ranolazine		Placebo
Arm/Group Description	Ranolazine 500mg by mouth twice per day and after two weeks increase to 1000mg by mouth twice per day Ranolazine: Ranolazine 500mg by mouth twice per day and after two weeks increases 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
All Cause Mortality
	Ranolazine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		1/8 (12.5%)
Serious Adverse Events
	Ranolazine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/14 (21.4%)		2/8 (25%)
Cardiac disorders
heart failure	3/14 (21.4%)	3	2/8 (25%)	2
Other (Not Including Serious) Adverse Events
	Ranolazine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/14 (78.6%)		4/8 (50%)
Gastrointestinal disorders
nausea	2/14 (14.3%)	2	0/8 (0%)	0
dyspepsia	0/14 (0%)	0	1/8 (12.5%)	1
loss of appetite	1/14 (7.1%)	1	0/8 (0%)	0
bloating	1/14 (7.1%)	1	0/8 (0%)	0
dry mouth	1/14 (7.1%)	1	0/8 (0%)	0
General disorders
fatique	1/14 (7.1%)	1	0/8 (0%)	0
Musculoskeletal and connective tissue disorders
leg weakness	1/14 (7.1%)	1	0/8 (0%)	0
muscle spasm	1/14 (7.1%)	1	0/8 (0%)	0
TENOSYNOVITIS,	1/14 (7.1%)	1	0/8 (0%)	0
Nervous system disorders
restless sleep	1/14 (7.1%)	1	0/8 (0%)	0
Renal and urinary disorders
dark urine	1/14 (7.1%)	1	0/8 (0%)	0
Respiratory, thoracic and mediastinal disorders
dryness on CPAP	0/14 (0%)	0	1/8 (12.5%)	1
cold	0/14 (0%)	0	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
hair loss	0/14 (0%)	0	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.