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To Compare the Efficacy of Combination Therapy vs Monotherapy for Pulmonary Arterial Hypertension in Systemic Sclerosis (BosSilSS)

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ClinicalTrials.gov Identifier: NCT03053739
Recruitment Status : Unknown
Verified February 2017 by DR PREKSHA DWIVEDI, Postgraduate Institute of Medical Education and Research.
Recruitment status was:  Recruiting
First Posted : February 15, 2017
Last Update Posted : February 15, 2017
Sponsor:
Information provided by (Responsible Party):
DR PREKSHA DWIVEDI, Postgraduate Institute of Medical Education and Research

Brief Summary:
The study will be carried out on 50 consecutive consenting patients of systemic sclerosis with PAH recruited from outpatient department of internal medicine and rheumatology clinic of PGIMER, Chandigarh, India It is a single centre double blind randomised controlled trial evaluating the effect of upfront dual therapy (sildenafil and bosentan) vs monotherapy (sildenafil) Participants will be randomised in 1:1 ratio to one of treatment arms. Placebo and PDE-5 inhibitors 20 mg BD to 60 mg if patient tolerates the drug well to one study arm and PDE-5 inhibitors plus ER antagonist 62.5 to max of 125 to other study group

Condition or disease Intervention/treatment Phase
Associated Pulmonary Arterial Hypertension Drug: Sildenafil 20mg and Bosentan 62.5mg Drug: Sildenafil 20mg and Placebo Phase 4

Detailed Description:

All patients fulfilling the SSc classification criteria of American College of Rheumatology during the study period will be screened for presence of PAH. Diagnosed cases of PAH based on CD echo with PAP >35mmHg based on echocardiography will be enrolled in study.Baseline NYHA functional class and 6 min walk distance in meters will be assessed. Heamogram and LFT will be measured Patients will be assessed at two weeks for side effects/safety issues. 6MWT and NYHA functional class will be reassessed at 3 months and 6 months.2D echo will be done at 6 months to measure mPAP RandomizationAll eligible patients will be randomized in a 1:1 ratio in blocks of ten between the two arms. Randomization will be stratified based on severity of PAH. The drugs will be labelled as A and B randomly by another staff member, who will not be involved in deciding the treatment of the study subjects. The randomization sequence will be generated using computer random number generator.

Blinding will be ensured by matching placebo for ERA in one group and will labelled one treatment arm as 'A' and other treatment arm as 'B'. Allocation concealment will be ensured by means of enclosing the randomization sequence in sealed opaque envelopes. Sealed opaque envelopes will contain Code 'A' or Code 'B'.

Intervention-The study consists of two treatment arms. The study drugs mainly Bosentan and Placebo will be packed into matching tablets at the dosage 62.5 mg. One treatment arm will contain Sildenafil and Placebo while other treatment arm will contain Sildenafil and Bosentan. Treatment will be initiated as 20 mg twice a day for Sildena-fil in combination with placebo once a day in one treatment arm and with Bosentan 62.5 mg once a day in other treatment arm .Dose of Sildenafil will be increased to 20 mg thrice a day at four weeks and that of Bosentan to 62.5 mg twice a day. Placebo will be also be provided twice a day.This will be continued till end of study period.. Dose adjustments in case of adverse events will be made depending on the severity of adverse events.

Statistical analysis- Intention to treat analysis will be carried for the primary and secondary outcomes. For continuous outcomes, unpaired t-test and for dichotomous outcomes chi-squares test with Yate's correction will be used. P<0.05 will be considered significant


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial to Compare the Efficacy of Combination Therapy vs Monotherapy for Pulmonary Arterial Hypertension in Systemic Sclerosis
Study Start Date : December 2016
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017


Arm Intervention/treatment
Active Comparator: Combination arm A-Sildenafil and Bosentan

Combination Arm A -Intervention- Drug

  • Tab Sildenafil 20 mg - three times a day for 6 months,and
  • Tab Bosentan 62.5mg - twice a day for 6 months
Drug: Sildenafil 20mg and Bosentan 62.5mg
Sildenafil 20 mg three times a day and bosentan 62.5mg two times a day

Placebo Comparator: Monotherapy arm-Sildenafil and Placebo
Monotherapy arm B Intervention-Drugs Tab Sildenafil 20mg- three times a day for 6 months, and Placebo tab (matched for bosentan) for 6 months
Drug: Sildenafil 20mg and Placebo
Sildenafil 20 mg three times a day and placebo (matched for bosentan)two times a day




Primary Outcome Measures :
  1. Change in Pulmonary artery pressures [ Time Frame: Baseline and 6 months ]
    Change in Pulmonary artery pressures measured by echocardiography at baseline and 6 months in patients of systemic sclerosis with PAH when treatment with Single(PDE-5inhibitors at dose of 20 mg maximum upto 60mg) versus Dual therapy(PDE-5inhibitors and ER antagonist 62.5 mg maximum upto 125mg) for 6 months


Secondary Outcome Measures :
  1. 1.Change in 6 Minute walk distance [ Time Frame: Baseline and 6 months ]
    1. To compare change in 6 MWD at baseline, and 6 months when treated with single versus dual therapy.

  2. Time To Clinical Worsening (TTCW) [ Time Frame: Baseline and 6 months ]
    To compare time to clinical worsening (TTCW) in SSc patients when treated with single versus dual therapy. TTCW is defined as first occurrence of all cause deaths, PAH related hospitalisation, worsening of symptoms defined as a decrease of >15% in 6 min walk distance and worsening of NYHA functional class.

  3. Emergent side effects of Sildenafil and Bosentan [ Time Frame: Baseline to 6 months ]
    To compare the emergent side effects of sildenafil and bosentan by way of comparison of serious and nonserious side effects.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients aged 18 years
  • Patients with systemic sclerosis
  • PAH diagnosed as PAP>35mmHg
  • NYHA functional class II,III,IV
  • SSc disease duration >1years

Exclusion Criteria:

  • Forced vital capacity <60% predicted
  • Renal insufficiency
  • Left heart disease and other relevant cardiac conditions
  • Pregnant or breastfeeding female
  • Patients on PAH specific therapy
  • Liver disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03053739


Contacts
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Contact: Preksha Dwivedi, M D +91-8109492343 drpreksha07@gmail.com
Contact: Shefali Sharma, M.D +91-9417372439 sharmashefali@hotmail.com

Locations
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India
Dr Preksha Dwivedi Recruiting
Chandigarh, India, 160012
Contact: Preksha Dwivedi, MD    +91-8109492343    drpreksha07@gmail.com   
Contact: Shefali Sharma, MD    +91-9417372439    Sharmashefali@hotmail.com   
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
Investigators
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Study Chair: Nandita Kakker, M.D Institutional ethics committee,PGIMER Chandigarh,India

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Responsible Party: DR PREKSHA DWIVEDI, SENIOR RESIDENT,CLINICAL IMMUNOLOGY AND RHEUMATOLOGY ,DEPT OF INTERNAL MEDICINE, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT03053739     History of Changes
Other Study ID Numbers: MK/2927/DM/9430
First Posted: February 15, 2017    Key Record Dates
Last Update Posted: February 15, 2017
Last Verified: February 2017

Keywords provided by DR PREKSHA DWIVEDI, Postgraduate Institute of Medical Education and Research:
Systemic sclerosis, Associated Pulmonary Arterial Hypertension

Additional relevant MeSH terms:
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Hypertension
Sclerosis
Familial Primary Pulmonary Hypertension
Scleroderma, Systemic
Scleroderma, Diffuse
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Connective Tissue Diseases
Skin Diseases
Sildenafil Citrate
Bosentan
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents
Antihypertensive Agents
Endothelin Receptor Antagonists