Trial Outcomes & Findings for Study of Ranolazine in the Treatment of Pulmonary Hypertension Associated With Diastolic Left Ventricular Dysfunction (NCT NCT02133352)

Last Updated: 2017-05-17

Results Overview

Assess the percent change in mPAP, PAOP and pulmonary vascular resistance (PVR) by RHC. Additional RHC completed at optional follow up for patients remaining on ranolazine upon completion of 180 day period.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

10 participants

Primary outcome timeframe

180 days

Results posted on

2017-05-17

Participant Flow

Participant milestones

Participant milestones
Measure	Ranolazine Ranolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine: open label/Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
Main Study (180 Day) STARTED	10
Main Study (180 Day) COMPLETED	10
Main Study (180 Day) NOT COMPLETED	0
Longer Term Extension STARTED	10
Longer Term Extension COMPLETED	4
Longer Term Extension NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Ranolazine Ranolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine: open label/Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
Longer Term Extension 4 of the initial 10 subjects agreed/cons	6

Baseline Characteristics

Study of Ranolazine in the Treatment of Pulmonary Hypertension Associated With Diastolic Left Ventricular Dysfunction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ranolazine n=10 Participants Ranolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine: Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
Age, Continuous	62.8 years STANDARD_DEVIATION 6.1 • n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants

PRIMARY outcome

Timeframe: 180 days

Population: We hypothesize that patients with pulmonary hypertension associated with diastolic left ventricular dysfunction treated with Ranolazine (initiated at 500 mg twice daily and increased to 1000mg twice daily) would have improved hemodynamic parameters, functional capacity and exercise tolerance compared to baseline.

Outcome measures

Outcome measures
Measure	Ranolazine n=10 Participants Ranolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine: open label/Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
Percent Change in mPAP, PAOP and Pulmonary Vascular Resistance (PVR) % Change in mPAP	-21 percentage change Standard Deviation 7.43
Percent Change in mPAP, PAOP and Pulmonary Vascular Resistance (PVR) % Change in PAOP	-39 percentage change Standard Deviation 7.28
Percent Change in mPAP, PAOP and Pulmonary Vascular Resistance (PVR) % Change in PVR	-4.0 percentage change Standard Deviation 153.86

SECONDARY outcome

Timeframe: 180 days

Assess % change in other hemodynamic parameters, by RHC, from baseline afeter 180 days of ranolazine. Right atrial pressure (RAP) Systolic pulmonary artery pressure (SPAP) Diastolic pulmonary artery pressure (DPAP) Cardiac output (CO) Cardiac index (CI)

Outcome measures

Outcome measures
Measure	Ranolazine n=10 Participants Ranolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine: open label/Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
Percent Change in Other Hemodynamic Parameters RAP	-56 percent change Standard Deviation 4.59
Percent Change in Other Hemodynamic Parameters SPAP	-12 percent change Standard Deviation 11.41
Percent Change in Other Hemodynamic Parameters DPAP	-33 percent change Standard Deviation 5.79
Percent Change in Other Hemodynamic Parameters CO	22 percent change Standard Deviation 1.78
Percent Change in Other Hemodynamic Parameters CI	24 percent change Standard Deviation 0.87

SECONDARY outcome

Timeframe: 180 days

Assess the change from baseline in 6 minute walk test (6MWT) after 180 days of twice daily ranolazine Optional follow up for some patients also includes 6MWT.

Outcome measures

Outcome measures
Measure	Ranolazine n=10 Participants Ranolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine: open label/Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
6 Minute Walk Test (6MWT)	33.7 meters Standard Deviation 35.17

SECONDARY outcome

Timeframe: 180 days

Assess changes from baseline in measurements of cardiac size and function obtained by MRI after 180 days of twice daily ranolazine. An additional MRI may be completed at optional follow up visit for patients continuing on ranolazine following completion of the 180 day treatment period.

Outcome measures

Outcome measures
Measure	Ranolazine n=5 Participants Ranolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine: open label/Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
Change in Cardiac Size and Function RVEF	3 % ejection fraction Standard Deviation .88
Change in Cardiac Size and Function LVEF	5.4 % ejection fraction Standard Deviation .2

SECONDARY outcome

Timeframe: 180 days

To assess the changes from baseline in echocardiographic parameters (left ventricular geometry and function, LVEF, evidence of diastolic dysfunction, SPAP, right ventricular geometry and function, degree of tricuspid regurgitation) after 180 days of twice daily ranolazine. An additional echo may be completed at optional follow up visit for patients continuing on ranolazine following completion of the 180 day treatment period.

Outcome measures

Outcome measures
Measure	Ranolazine n=6 Participants Ranolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine: open label/Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
Change in Echocardiogram Parameters (LVEF)	.67 LVEF % Standard Deviation 1.9

SECONDARY outcome

Timeframe: 180 days

Assess the change from baseline in BNP cardiac biomarkers after 180 days of twice daily ranolazine. Cardiac biomarkers may be completed at optional follow up visit for patients continuing on ranolazine following completion of the 180 day treatment period.

Outcome measures

Outcome measures
Measure	Ranolazine n=10 Participants Ranolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine: open label/Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
Change in BNP Cardiac Biomarker	32.1 pg/mL Standard Deviation 5.2

Adverse Events

Ranolazine

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ranolazine n=10 participants at risk Ranolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine: Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
Cardiac disorders Bradycardia with junctional ventricular escapes	10.0% 1/10 • Number of events 1 • 180 Days
Gastrointestinal disorders GI bleed	10.0% 1/10 • Number of events 1 • 180 Days
Cardiac disorders CHF Exacerbation	10.0% 1/10 • Number of events 1 • 180 Days
Cardiac disorders Chest pain	10.0% 1/10 • Number of events 1 • 180 Days

Other adverse events

Other adverse events
Measure	Ranolazine n=10 participants at risk Ranolazine- initiated at 500mg twice daily and increased to 1000mg twice daily as tolerated after 2wks; the tolerated dose will be used for the remainder of the Treatment Period. Ranolazine: Single arm- ranolazine, initiated at 500 mg BID and increased to 1000 mg BID as tolerated
Gastrointestinal disorders diarrhea	10.0% 1/10 • Number of events 1 • 180 Days
Respiratory, thoracic and mediastinal disorders increased shortness of breath	10.0% 1/10 • Number of events 1 • 180 Days
General disorders difficulty concentrating	10.0% 1/10 • Number of events 1 • 180 Days
General disorders patient fall	10.0% 1/10 • Number of events 1 • 180 Days
Immune system disorders worsening foot pain/gout	10.0% 1/10 • Number of events 1 • 180 Days
General disorders common cold	40.0% 4/10 • Number of events 7 • 180 Days
Gastrointestinal disorders increased stomach discomfort	10.0% 1/10 • Number of events 1 • 180 Days
Infections and infestations urinary tract infection	10.0% 1/10 • Number of events 1 • 180 Days
General disorders lightheadedness	30.0% 3/10 • Number of events 4 • 180 Days
Endocrine disorders elevated blood sugar	10.0% 1/10 • Number of events 1 • 180 Days
Gastrointestinal disorders nausea	30.0% 3/10 • Number of events 4 • 180 Days
General disorders increased fatigue	10.0% 1/10 • Number of events 1 • 180 Days
General disorders sore throat	10.0% 1/10 • Number of events 1 • 180 Days
General disorders muscle spasm	10.0% 1/10 • Number of events 1 • 180 Days
Infections and infestations kidney infection	10.0% 1/10 • Number of events 1 • 180 Days
Musculoskeletal and connective tissue disorders intermittent increased back pain	10.0% 1/10 • Number of events 1 • 180 Days
Musculoskeletal and connective tissue disorders knee pain	10.0% 1/10 • Number of events 1 • 180 Days
General disorders buttocks/upper leg pain	10.0% 1/10 • Number of events 1 • 180 Days
General disorders thumb pain	10.0% 1/10 • Number of events 1 • 180 Days

Additional Information

Kimberly Finch

Boston University

Phone: 617-638-4475

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place