Associated Pulmonary Arterial HypertensionPhase 4BosSilSSNCT03053739
To Compare the Efficacy of Combination Therapy vs Monotherapy for Pulmonary Arterial Hypertension in Systemic Sclerosis
A Phase 4 study testing Sildenafil 20mg and Bosentan 62.5mg in people with Associated Pulmonary Arterial Hypertension, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Associated Pulmonary Arterial Hypertension
- What is being tested?
- Sildenafil 20mg and Bosentan 62.5mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteIndia
- Study dates
- Dec 2016to Dec 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Dr Preksha Dwivedi
Chandigarh, 160012
Preksha Dwivedi, MD, +91-8109492343, drpreksha07@gmail.com
Shefali Sharma, MD, +91-9417372439, Sharmashefali@hotmail.com
About this study
Official title: Randomized Controlled Trial to Compare the Efficacy of Combination Therapy vs Monotherapy for Pulmonary Arterial Hypertension in Systemic Sclerosis
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
Read the 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
- Being tested
- Sildenafil 20mg and Bosentan 62.5mg, Sildenafil 20mg and Placebo
- Keywords
- Systemic sclerosis, Associated Pulmonary Arterial Hypertension
- Medical subject headings
- Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil 20mg and Bosentan 62.5mgDrug
Sildenafil 20 mg three times a day and bosentan 62.5mg two times a day
Sildenafil 20mg and PlaceboDrug
Sildenafil 20 mg three times a day and placebo (matched for bosentan)two times a day
| Study group | Role | What they receive |
|---|---|---|
| Combination arm A-Sildenafil and Bosentan | Active comparator | 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 Receives: Drug: Sildenafil 20mg and Bosentan 62.5mg |
| Monotherapy arm-Sildenafil and Placebo | Placebo comparator | Monotherapy arm B Intervention-Drugs Tab Sildenafil 20mg- three times a day for 6 months, and Placebo tab (matched for bosentan) for 6 months Receives: Drug: Sildenafil 20mg and Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pulmonary artery pressures
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
Measured: Baseline and 6 months
Secondary outcomes (3)
1.Change in 6 Minute walk distance
- To compare change in 6 MWD at baseline, and 6 months when treated with single versus dual therapy.
Measured: Baseline and 6 months
Time To Clinical Worsening (TTCW)
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.
Measured: Baseline and 6 months
Emergent side effects of Sildenafil and Bosentan
To compare the emergent side effects of sildenafil and bosentan by way of comparison of serious and nonserious side effects.
Measured: Baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2017
- Study startDec 2016
- Primary completionDec 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Associated Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, DR PREKSHA DWIVEDI, Post Graduate Institute of Medical Education and Research, Chandigarh
- Investigators
- Nandita Kakker, M.D, Study chair, Institutional ethics committee,PGIMER Chandigarh,India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03053739
- Sponsor's protocol ID
- MK/2927/DM/9430
- Acronym
- BosSilSS
- Status last verified
- Feb 2017
- First submitted
- 29 Dec 2016
- Last updated
- 15 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial to Compare the Efficacy of Combination Therapy vs Monotherapy for Pulmonary Arterial Hypertension in Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT03053739
- Acronym / sponsor ID
- BosSilSS / MK/2927/DM/9430
- Keywords
- Systemic sclerosis, Associated Pulmonary Arterial Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- Dec 2016
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 15 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Combination arm A-Sildenafil and Bosentan | Active comparator | Drug: Sildenafil 20mg and Bosentan 62.5mgCombination 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 |
| Monotherapy arm-Sildenafil and Placebo | Placebo comparator | Drug: Sildenafil 20mg and PlaceboMonotherapy arm B Intervention-Drugs Tab Sildenafil 20mg- three times a day for 6 months, and Placebo tab (matched for bosentan) for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- Forced vital capacity <60% predicted
- Renal insufficiency
- Left heart disease and other relevant cardiac conditions
- Pregnant or breastfeeding female
- Patients on PAH specific therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sildenafil 20mg and Bosentan 62.5mgSildenafil 20 mg three times a day and bosentan 62.5mg two times a day | Drug | Combination arm A-Sildenafil and Bosentan |
| Sildenafil 20mg and PlaceboSildenafil 20 mg three times a day and placebo (matched for bosentan)two times a day | Drug | Monotherapy arm-Sildenafil and Placebo |
Primary outcome
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
3 secondary outcomes
1.Change in 6 Minute walk distance
Time frame: Baseline and 6 months
Time To Clinical Worsening (TTCW)
Time frame: Baseline and 6 months
Emergent side effects of Sildenafil and Bosentan
Time frame: Baseline to 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nandita Kakker, M.D study chair
Institutional ethics committee,PGIMER Chandigarh,India
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sildenafil 20mg and Bosentan 62.5mg in people with Associated Pulmonary Arterial Hypertension, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Preksha Dwivedi, M D (+91-8109492343, drpreksha07@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pulmonary artery pressures (time frame: Baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2017.