Safety and Efficacy of Terbogrel in Patients With Primary Pulmonary Hypertension

Study Overview
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Brief Summary
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This study sought to determine whether terbogrel was an effective treatment for primary pulmonary hypertension (PPH) by comparing its efficacy and safety to that of placebo.

Official Title
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A Randomized, Double-blind, Placebo-controlled Evaluation of the Safety and Efficacy of Terbogrel in Patients With Primary Pulmonary Hypertension

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Drug: Terbogrel low dose
* Drug: Terbogrel high dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary pulmonary hypertension and New York Health Association (NYHA) chronic heart failure (CHF) functional class II-III Ability to walk >= 50 meters on the 6 minute walk test Resting mean pulmonary artery pressure > 25 mmHg Mean right atrial pressure <= 20 mmHg Pulmonary capillary wedge pressure <= 15 mmHg Cardiac index > 2.5 L/min2 SvO2 sat. > 63% Male of female at least 18 years old Signed written informed consent Exclusion Criteria: Secondary pulmonary hypertension due to lung or systemic diseases Pregnant of nursing women, or women of childbearing potential who are not using adequate methods of birth control Concurrent systematic use of aspirin, aspirin like drugs, or non-steroidal anti-inflammatory drugs (NSAIDs) Surgery of bleeding from gastrointestinal, genitourinary tract, cerebrum or retina within past 6 weeks History of bleeding diathesis or a platelet count less than 70,000/mm3 Exercise limited by factors other than fatigue or exertional dyspnea, such as arthritis, claudication, angina, chronic obstructive pulmonary disease, or bronchial asthma Myocardial infarction, stroke, or transient ischemic attack within the preceding six months Systolic blood pressure < 90 mmHg or > 180 mmHg, or diastolic blood pressure > 110 mmHg Known drug or alcohol dependency within one year of entry into the study Known hypersensitivity to any component of the study formulation, epoprostenol, nitric oxide, or adenosine Psychiatric or other illness or condition which, in the opinion of the principal investigator, may interfere with study participation, compliance, or other elements of the protocol Participation in an evaluation of an investigational drug within the past 30 days Portal hypertension or cirrhosis of the liver Congenital heart disease e.g., atrial septal defect; patent foramen ovale does not exclude patient from the study Appetite suppressants such as fenfluramine, dexfenfluramine, and inhibitors of serotonin uptake known to be associated with primary pulmonary hypertension, received within 3 months of entry into the study HIV positive Vasodilators. Patients will not receive Ca-channel blockers during the study unless the medication was started prior to the study and the patient has been on a stable dose for at least one month prior to entry

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Terbogrel low dose<br> | Drug: Terbogrel low dose<br> <br> |
| Experimental: Terbogrel high dose<br> | Drug: Terbogrel high dose<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in distance walked in 6 minutes |  | baseline, after 3 months of treatment | 
| Change in pulmonary vascular resistance (PVR) |  | baseline, after 3 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pulmonary artery pressure (PAP) |  | baseline, after 3 months of treatment | 
| Change in cardiac index (CI) |  | baseline, after 3 months of treatment | 
| Change in venous oxygen saturation (SvO2 sat.) |  | baseline, after 3 months of treatment | 
| Change in quality of life by SF-36 questionnaire |  | baseline, after 3 months of treatment | 
| Change in chronic heart failure index | questionnaire | baseline, after 3 months of treatment | 
| Change in dyspnea/fatigue rating |  | baseline, after 3 months of treatment |