Comparison of Efficacy Different Treatment Regimens in Pulmonary Hypertension Secondary to Lung Disease and or Hypoxia

Study Overview
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Brief Summary
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This is an open label, randomized, interventional study indented to find the efficacy of different treatment regimens in treatment of pulmonary hypertension secondary to lung disease and/or hypoxia.This is to find out when to start combination therapy (sildenafil plus bosentan) in treatment of pulmonary hypertension secondary to lung disease and/or hypoxia.

Detailed Description
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This is an open label, randomized, interventional study indented to find the efficacy of different treatment regimens in treatment of pulmonary hypertension secondary to lung disease and/or hypoxia. It involves 3 arms, one getting monotherapy with sildenafil for 6 months, 2nd getting bosentan monotherapy initially for 3 months and then combination of sildenafil and bosentan for 3 months, 3rd getting combination sildenafil and bosentan from the beginning for 6 months. The aim is to decide when is the best time to start combination therapy either from start or at the time of drug failure. Improvement will be assessed by change in functional class, pulmonary pressures measured by ECHO, pulmonary function test, six minute walk test and biochemical markers. Lack of randomized trials and Indian data is there on the subject. Also adverse events and serious adverse events will be closely monitored and reported to the ethics committee and DCGI immediately.

Official Title
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Comparison of Efficacy Different Treatment Regimens in Pulmonary Hypertension Secondary to Lung Disease and or Hypoxia

Conditions
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Pulmonary Hypertension Secondary to Lung Disease and/or Hypoxia

Intervention / Treatment
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* Drug: Sildenafil
* Drug: Bosentan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pulmonary artery hypertension diagnosed by doppler echocardiography as mean pulmonary artery pressure 25 mmHg (done in department of cardiology, AIIMS) Age more than 18 years Pulmonary artery hypertension due to hypoxia, either chronic obstructive airway disease or diffuse pulmonary lung disease Willing to consent to participate in the trial WHO functional class I,II, III Exclusion Criteria: WHO functional class IV Patient participating in any other trial Concomitant coronary artery disease Nitrate intake Liver dysfunction Pregnancy and lactation -

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Monotherapy<br>Sildenafil will be started at 20mg OD and then increased to 20mg TDS if there is no fall in BP. Total duration is of 6 months | Drug: Sildenafil<br>* 20 mg initially and then increased to 20 mg TDS if there is no fall in BP<br>|
| Active Comparator: Sequential Therapy<br>Bosentan will be started at 62.5mg BD for 4 weeks and then increased to 125mg BD. Sildenafil will be started be added after 3 months. Sildenafil will be started at 20mg OD and then increased to 20mg TDS if there is no fall in BP. Total duration is of 6 months. Bosentan and sildenafil will be in combination in the last 3 months. No fixed dose combination will be used. | Drug: Sildenafil<br>* 20 mg initially and then increased to 20 mg TDS if there is no fall in BP<br>Drug: Bosentan<br>* Bosentan 62.5 mg BD initially for 1 month and then increased to 125 mg BD<br>|
| Active Comparator: Combination therapy<br>Bosentan will be started at 62.5mg BD for 4 weeks and then increased to 125mg BD. Sildenafil will be started at 20mg OD and then increased to 20mg TDS if there is no fall in BP. Total duration is of 6 months. No fixed dose combination will be used. | Drug: Sildenafil<br>* 20 mg initially and then increased to 20 mg TDS if there is no fall in BP<br>Drug: Bosentan<br>* Bosentan 62.5 mg BD initially for 1 month and then increased to 125 mg BD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echocardiogram | Improvement in pulmonary artery pressures | 6 months | 
| WHO functional classification | Improvement in WHO functional classification | 6 months | 
| 6 minute walk test | Improvement in 6 minute walk test | 6 months | 
| Pulmonary function test | Improvement in Pulmonary function test | 6 months | 
| Visual analog scale for dyspnea | Improvement in Visual analog scale for dyspnea | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echocardiography measuring pulmonary artery pressure | Improvement in pulmonary artery pressures measured by Echocardiography | 3 months | 
| WHO functional classification | Improvement in WHO functional classification | 3 months | 
| 6 minute walk test | Improvement in 6 minute walk test | 3 months | 
| Pulmonary function test | Improvement in Pulmonary function test | 3 months | 
| Visual analog scale for dyspnea | Improvement in Visual analog scale for dyspnea | 3 months | 
| Biochemical markers at 3 and 6 months | Levels of biomarkers such as Trop T, pro-BNP, uric acid at 3 months and 6 months after starting the drugs | 6 months | 
| Monitoring side effects of the drugs | adverse events and serious adverse events will be closely monitored and reported to the ethics committee and DCGI immediately | 6 months |