RHYME: Ranolazine for the Treatment of Chest Pain in HCM Patients

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01721967
• Collaborator: Gilead Sciences (Industry)
• Enrollment: 14
• Location: 1
• Arm: 1
• Duration (Months): 42
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of RHYME is to evaluate the safety and efficacy of ranolazine in Hypertrophic Cardiomypathy patients with chest pain or dyspnea despite treatment with standard medical therapy. This is a small, pilot, open-label (non-randomized) study of an approved drug for the treatment of angina in a novel patient population (adult patient population with hypertrophic cardiomyopathy).

Condition or Disease	Intervention/Treatment	Phase
Hypertrophic Cardiomyopathy	Drug: Ranolazine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Ranolazine for the Treatment of Angina in Hypertrophic Cardiomyopathy Investigation
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ranolazine Ranolazine, 500 mg for 60 days	Drug: Ranolazine; Other Names: Ranexa

Outcome Measures

Primary Outcome Measures

1. QT Interval [60 Days]

2. Number of Adverse Events Considered Probably or Possibly Related to Study Drug [60 Days]

   Number of events that are considered probably or possibly related to study drug.

3. Drug Tolerability [60 days]

   Total number of patients that tolerated 1,000mg BID dose and 500 mg BID dose

Secondary Outcome Measures

1. Improvement in Number of Episodes of Angina Per Week [Baseline and 60 Days post treatment]

   Efficacy of ranolazine in HCM patients with respect to improvements in angina frequency (number of episodes of angina per week).

2. Seattle Angina Questionnaire (SAQ) [60 Days post treatment]

   The Seattle Angina Questionnaire (SAQ) is a self-administered, 19-item questionnaire, a cardiac disease-related quality-of-life measure. The SAQ is well validated and sensitive to clinical changes. It has five subscales: physical limitation, angina stability, angina frequency, treatment satisfaction, and disease perception. The possible range of scores for each of the five subscales is 0 to 100, with higher scores indicating better quality of life.

3. Kansas City Cardiomyopathy Questionnaire (KCCQ) [60 days post treatement]

   Kansas City Cardiomyopathy Questionnaire (KCCQ) (scores range from 0 to 100 with higher scores representative of a higher quality of life; clinically important changes are considered > 10 points and >5 points, respectively, as previously established

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18 years or older

• Left Ventricle wall thickness >/= 15mm in the absence of other condition causing hypertrophy

• Baseline Angina/Shortness of Breath Frequency of > 2 episodes per week

• Willing to provide informed consent

Exclusion Criteria:

• Severe stenotic valvular disease

• Severe valvular regurgitation except mitral regurgitation due to systolic anterior motion

• Significant (>60% stenosis) coronary artery disease

• Acute coronary syndrome within 30 days

• Severe heart failure defined as LV systolic dysfunction with Ejection Fraction <40% or NYHA class 4 symptoms

• Severe renal impairment (glomerular filtration rate, <30 mL/min/1.73 m2)

• Moderate-severe hepatic impairment (Child-Pugh classes B and C)

• Hospitalization for cardiac reason within 3 months of enrollment

• Anticipated changes to treatment of HCM within study period, including medications, device implantation, or septal reduction therapies

• Concomitant use of ketoconazole, macrolide antibiotics, and HIV protease inhibitors

• Active myocarditis, pericarditis, or restrictive cardiomyopathy

• Non-cardiac terminal illness with expected survival less than 6 months

• Women who are of childbearing potential

• Inability to perform or adhere to study protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University
• Gilead Sciences

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT01721967
• Other Study ID Numbers: Pro00039302; 3938381
• First Posted: Nov 6, 2012
• Last Update Posted: Mar 3, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Duke University: chest pain; dyspnea
• Additional relevant MeSH terms: Cardiomyopathies; Cardiomyopathy, Hypertrophic; Hypertrophy; Ranolazine

Study Results

Participant Flow

Arm/Group Title	Ranolazine
Arm/Group Description	Ranolazine, 500 mg for 60 days
Period Title: Overall Study
STARTED	14
COMPLETED	11
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Ranolazine
Arm/Group Description	Ranolazine, 500 mg for 60 days
Overall Participants	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.2 (9.0)
Sex: Female, Male (Count of Participants)
Female	8 57.1%
Male	6 42.9%
Seattle Angina Questionnaire (units on a scale) [Mean (Standard Deviation) ]
Physical limitation	49.6 (18.7)
Anginal stability	45.5 (27.0)
Anginal frequency	65.5 (13.4)
Treatment satisfaction	85.2 (12.6)
Quality of life	40.9 (24.6)
Kansas City Cardiomyopathy Questionnaire (KCCQ) (units on a scale) [Mean (Standard Deviation) ]
Physical limitation	61.7 (20.6)
Symptom stability	43.2 (16.2)
Symptom frequency	56.4 (20.6)
Symptom burden	55.3 (29.4)
Total symptom score	55.9 (24.2)
Self-efficacy	78.4 (21.7)
Quality of life	39.4 (26.6)
Social limitation	46.0 (31.5)
Overall summary	51.2 (22.3)
Clinical summary	58.8 (20.9)

Outcome Measures

1. Primary Outcome

Title	QT Interval
Time Frame	60 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranolazine
Arm/Group Description	Ranolazine, 500 mg for 60 days
Measure Participants	11
Mean (Standard Deviation) [msec]	462.8 (27.4)

2. Primary Outcome

Title	Number of Adverse Events Considered Probably or Possibly Related to Study Drug
Description	Number of events that are considered probably or possibly related to study drug.
Time Frame	60 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranolazine
Arm/Group Description	Ranolazine, 500 mg for 60 days
Measure Participants	14
Number [adverse event]	10

3. Primary Outcome

Title	Drug Tolerability
Description	Total number of patients that tolerated 1,000mg BID dose and 500 mg BID dose
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranolazine
Arm/Group Description	Ranolazine, 500 mg for 60 days
Measure Participants	14
1000 mg BID	9 64.3%
500 mg BID	4 28.6%

4. Secondary Outcome

Title	Improvement in Number of Episodes of Angina Per Week
Description	Efficacy of ranolazine in HCM patients with respect to improvements in angina frequency (number of episodes of angina per week).
Time Frame	Baseline and 60 Days post treatment

Outcome Measure Data

Analysis Population Description

episodes of angina per week was not collected

Arm/Group Title	Ranolazine
Arm/Group Description	Ranolazine, 500 mg for 60 days
Measure Participants	0

5. Secondary Outcome

Title	Seattle Angina Questionnaire (SAQ)
Description	The Seattle Angina Questionnaire (SAQ) is a self-administered, 19-item questionnaire, a cardiac disease-related quality-of-life measure. The SAQ is well validated and sensitive to clinical changes. It has five subscales: physical limitation, angina stability, angina frequency, treatment satisfaction, and disease perception. The possible range of scores for each of the five subscales is 0 to 100, with higher scores indicating better quality of life.
Time Frame	60 Days post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranolazine
Arm/Group Description	Ranolazine, 500 mg for 60 days
Measure Participants	11
Physical limitation	61.4 (18)
Anginal stability	90.0 (21.1)
Anginal frequency	86.0 (12.7)
Treatment satisfaction	90.6 (11.5)
Quality of life	70.8 (11.3)

6. Secondary Outcome

Title	Kansas City Cardiomyopathy Questionnaire (KCCQ)
Description	Kansas City Cardiomyopathy Questionnaire (KCCQ) (scores range from 0 to 100 with higher scores representative of a higher quality of life; clinically important changes are considered > 10 points and >5 points, respectively, as previously established
Time Frame	60 days post treatement

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranolazine
Arm/Group Description	Ranolazine, 500 mg for 60 days
Measure Participants	11
Physical limitation	72 (20.6)
Symptom stability	72.7 (26.1)
Symptom frequency	72.2 (20)
Symptom burden	75 (24.2)
Total symptom score	73.6 (21.3)
Self-efficacy	85.2 (14.6)
Quality of life	65.2 (25.8)
Social limitation	66.1 (31.2)
Overall summary	69.8 (23.5)
Clinical summary	74 (20.5)

Adverse Events

Arm/Group Title	Ranolazine
Arm/Group Description	Ranolazine, 500 mg for 60 days
All Cause Mortality
	Ranolazine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ranolazine
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Other (Not Including Serious) Adverse Events
	Ranolazine
	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)
General disorders
dizziness	1/14 (7.1%)
Musculoskeletal and connective tissue disorders
Leg Weakness	1/14 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.