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

Phase 4

• Conditions: Pulmonary Hypertension Secondary to Lung Disease and/or Hypoxia
• Interventions: Drug: Sildenafil; Drug: Bosentan

• Registration Number: NCT01449253
• Lead Sponsor: All India Institute of Medical Sciences, New Delhi

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-08
• Study First Submitted: 2011-10-07
• Study First Submitted QC: 2011-10-07
• Study First Posted: 2011-10-10
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-28
• Last Update Posted: 2013-01-29
• Primary Completion: 2013-07
• Study Completion: 2013-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Pulmonary artery hypertension diagnosed by doppler echocardiography as mean pulmonary artery pressure 25 mmHg (done in department of cardiology, AIIMS)
2. Age more than 18 years
3. Pulmonary artery hypertension due to hypoxia, either chronic obstructive airway disease or diffuse pulmonary lung disease
4. Willing to consent to participate in the trial
5. WHO functional class I,II, III

Exclusion Criteria

1. WHO functional class IV
2. Patient participating in any other trial
3. Concomitant coronary artery disease
4. Nitrate intake
5. Liver dysfunction
6. Pregnancy and lactation -

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Monotherapy	Sildenafil	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
Sequential Therapy	Sildenafil	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.
Sequential Therapy	Bosentan	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.
Combination therapy	Sildenafil	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.
Combination therapy	Bosentan	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.

Primary Outcome Measures

Name	Time	Method
Echocardiogram	6 months	Improvement in pulmonary artery pressures
WHO functional classification	6 months	Improvement in WHO functional classification
6 minute walk test	6 months	Improvement in 6 minute walk test
Pulmonary function test	6 months	Improvement in Pulmonary function test
Visual analog scale for dyspnea	6 months	Improvement in Visual analog scale for dyspnea

Secondary Outcome Measures

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

Trial Locations

Locations (1)

All India Institute Of Medical Sciences; 🇮🇳 New Delhi, Delhi, India