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

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.

Study Overview

• Status: Unknown
• Conditions: Pulmonary Hypertension Secondary to Lung Disease and/or Hypoxia
• Intervention / Treatment: Drug: Sildenafil; Drug: Bosentan

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110029
      • Recruiting
      • All India Institute of Medical Sciences
      • Contact: Sajal Ajmani, MBBS; Phone Number: 9873570408; Email: sajalajmani@gmail.com
      • Principal Investigator: Surendra K Sharma, MD, Ph D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: All India Institute of Medical Sciences, New Delhi
• Investigators: Principal Investigator: Surendra K. Sharma, MD,Ph.D, All India Institute of Medical Sciences, New Delhi

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): July 1, 2013
• Study Completion (Anticipated): July 1, 2013

Study Registration Dates

• First Submitted: October 7, 2011
• First Submitted That Met QC Criteria: October 7, 2011
• First Posted (Estimate): October 10, 2011

Study Record Updates

• Last Update Posted (Estimate): January 29, 2013
• Last Update Submitted That Met QC Criteria: January 28, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Neoplasms; Signs and Symptoms, Respiratory; Neoplastic Processes; Hypertension; Lung Diseases; Neoplasm Metastasis; Hypertension, Pulmonary; Hypoxia; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Endothelin Receptor Antagonists; Sildenafil Citrate; Bosentan
• Other Study ID Numbers: pulmonary hypertension