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

Sponsor

All India Institute of Medical Sciences, New Delhi (Other)

Overall Status

Unknown status

CT.gov ID

NCT01449253

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Hypertension Secondary to Lung Disease and/or Hypoxia	Drug: Sildenafil Drug: Bosentan	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2011

Anticipated Primary Completion Date :

Jul 1, 2013

Anticipated Study Completion Date :

Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Monotherapy 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 20 mg initially and then increased to 20 mg TDS if there is no fall in BP
Active Comparator: Sequential Therapy 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 20 mg initially and then increased to 20 mg TDS if there is no fall in BP Drug: Bosentan Bosentan 62.5 mg BD initially for 1 month and then increased to 125 mg BD
Active Comparator: Combination therapy 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 20 mg initially and then increased to 20 mg TDS if there is no fall in BP Drug: Bosentan Bosentan 62.5 mg BD initially for 1 month and then increased to 125 mg BD

Arm

Intervention/Treatment

Active Comparator: Monotherapy

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

20 mg initially and then increased to 20 mg TDS if there is no fall in BP

Active Comparator: Sequential Therapy

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

20 mg initially and then increased to 20 mg TDS if there is no fall in BP

Drug: Bosentan

Bosentan 62.5 mg BD initially for 1 month and then increased to 125 mg BD

Active Comparator: Combination therapy

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

20 mg initially and then increased to 20 mg TDS if there is no fall in BP

Drug: Bosentan

Bosentan 62.5 mg BD initially for 1 month and then increased to 125 mg BD

Outcome Measures

Primary Outcome Measures

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

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
6 minute walk test [3 months]
Improvement in 6 minute walk test
Pulmonary function test [3 months]
Improvement in Pulmonary function test
Visual analog scale for dyspnea [3 months]
Improvement in Visual analog scale for dyspnea
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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