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Sildenafil for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS)

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ClinicalTrials.gov Identifier: NCT04797286
Recruitment Status : Recruiting
First Posted : March 15, 2021
Last Update Posted : September 27, 2021
Sponsor:
Collaborator:
Louisiana State University Health Sciences Center in New Orleans
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
This is a Phase II randomized, double-blind, placebo-controlled trial of sildenafil in men and women with Scleroderma with mildly elevated pulmonary pressures (SSc-MEP) to determine whether sildenafil may be an effective treatment for SSc-MEP.

Condition or disease Intervention/treatment Phase
Scleroderma Mildly Elevated Pulmonary Pressures Drug: Sildenafil Other: Placebo Phase 2

Detailed Description:
Data shows that sildenafil (SIL) is an effective therapy in SSc-PAH. SIL has been safely used in many patients with various vascular and cardiovascular diseases over the past three decades. Randomized controlled trial data for SIL shows improvement in 6MWD, hemodynamics, and even evidence of cardiac remodeling in PAH and SSc-PAH patients. Based upon these data, SIL may be an effective therapy in SSc-MEP. This study will help determine whether sildenafil could be a good treatment for patients with scleroderma that have mildly elevated pulmonary pressures.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Sildenafil for Early Pulmonary Vascular Disease in Scleroderma
Actual Study Start Date : September 20, 2021
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : September 2024


Arm Intervention/treatment
Experimental: Sildenafil
Sildenafil 20 mg by mouth three(3) times each day
Drug: Sildenafil
Sildenafil 20 mg three times a day. This is the approved dose for the treatment of pulmonary arterial hypertension. It is being studied in this trial with a population who has mildly elevated pulmonary pressures.
Other Name: Revatio, Viagra

Placebo Comparator: Placebo
Placebo by mouth three(3) times each day
Other: Placebo
Oral pill placebo.




Primary Outcome Measures :
  1. Difference in change in distance walked in 6 minute walk test (6MWT) at 4 months [ Time Frame: Baseline and 4 months ]
    As assessed by change in 6 minute walk distance (6MWD) in feet (from baseline to 4 months) between the sildenafil group and the placebo group.


Secondary Outcome Measures :
  1. Difference in change in distance walked in 6MWT at 12 months [ Time Frame: Baseline and 12 months ]
    As assessed by change in 6 minute walk test distance in feet (from baseline to 12 months) between the sildenafil group and the placebo group.

  2. Difference in change in right ventricular function as assessed by cardiac MRI [ Time Frame: Baseline and 4 months ]
    As assessed by change in right ventricular function (normal/abnormal) on cardiac MRI.

  3. Difference in change in right ventricular function as assessed by cardiac MRI [ Time Frame: Baseline and 12 months ]
    As assessed by change in right ventricular function (normal/abnormal) on cardiac MRI.

  4. Difference in change in right ventricular function as assessed by invasive hemodynamics [ Time Frame: Baseline and 4 months ]
    As assessed by change in right ventricular function (normal/abnormal) on invasive hemodynamics.

  5. Difference in change in right ventricular function as assessed by invasive hemodynamics [ Time Frame: Baseline and 12 months ]
    As assessed by change in right ventricular function (normal/abnormal) on invasive hemodynamics.

  6. Difference in change in right ventricular function as assessed by echocardiography [ Time Frame: Baseline and 4 months ]
    As assessed by change in right ventricular function (normal/abnormal) on echocardiography.

  7. Difference in change in right ventricular function as assessed by echocardiography [ Time Frame: Baseline and 12 months ]
    As assessed by change in right ventricular function (normal/abnormal) on echocardiography.

  8. Difference in change in N-terminal pro b-type natriuretic peptide level [ Time Frame: Baseline, 4 months and 12 months ]
    As assessed by changes in plasma N-terminal pro b-type natriuretic peptide (NT-proBNP) level (pg/mL) between sildenafil and placebo groups at four months and twelve months.

  9. Difference in change in health related quality of life as assessed by the 36-Item Short Form Health Survey (SF36) questionnaire [ Time Frame: Baseline, 4 months and 12 months ]
    As assessed by changes in SF36 questionnaire between sildenafil and placebo groups at four months and twelve months. The SF36 yields a set of scaled scores in 8 domains, with higher numbers representing a better quality of life. Each scale is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. In step 2, items in the same scale are averaged together to create the 8 scale scores. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Hence, scale scores represent the average for all items in the scale that the respondent answered.

  10. Difference in change in health related quality of life as assessed by the emPHasis-10 health-related quality of life questionnaire (emPHasis-10). [ Time Frame: Baseline, 4 months and 12 months ]
    As assessed by changes in emPHasis-10 questionnaire between sildenafil and placebo groups. The Emphasis 10 score consists of 10 questions scored in a semantic 6-point scale (from 0 to 5), for a total maximum score of 50 (the higher the score, the worse the quality of life).

  11. Difference in safety profile as assessed by frequency of adverse events [ Time Frame: Ongoing until study closes, up to 4 years ]
    As assessed by frequency of adverse events between sildenafil and placebo groups.

  12. Difference in safety profile as assessed by severity of adverse events [ Time Frame: Ongoing until study closes, up to 4 years ]
    As assessed by severity of adverse events between sildenafil and placebo groups.



Information from the National Library of Medicine

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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:

  • Previous documentation of mean pulmonary artery pressure between 21 and 24 mm Hg with a pulmonary capillary wedge pressure (or left ventricular end-diastolic pressure) ≤ 15 mm Hg within six months before study entry.
  • Diagnosis of SSc according to 2013 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria.
  • Pulmonary function tests with forced expiratory volume in one second/forced vital capacity (FEV1/FVC) >50% AND either a) total lung capacity (TLC) or forced vital capacity (FVC) > 70% predicted or b) TLC or FVC between 60% and 70% predicted with no more than mild interstitial lung disease on computerized tomography scan of the chest on studies obtained within 6 months of enrollment.
  • Ventilation perfusion scan or computed tomography with intravenous contrast (CT angiogram) without evidence of chronic thromboembolism at anytime before study entry.
  • Ability to perform six minute walk testing without significant limitations in musculoskeletal function or coordination.
  • Informed consent.

Exclusion Criteria:

  • World Health Organization (WHO) Class IV functional status.
  • Systolic blood pressure less than 90 mmHg at screening visit prior to enrollment.
  • Clinically significant untreated sleep apnea.
  • Left-sided valvular disease (more than moderate mitral valve stenosis or insufficiency or aortic stenosis or insufficiency), pulmonary artery or valve stenosis, or ejection fraction < 45% on most recent echocardiography (within 1 year).
  • Use of Pulmonary Arterial Hypertension (PAH) therapy (prostacyclin analogues, endothelin-1 receptor antagonists,phosphodiesterase-5 inhibitors, riociguat, selexipag) within the past 3 months.
  • Hospitalized or acutely ill.
  • Renal failure (creatinine above 2.0) at screening visit.
  • Enrollment in a clinical trial or concurrent use of another investigational drug (non FDA approved) or device therapy within 30 days of screening visit.
  • Age < 18.
  • Currently pregnant.
  • Current use of nitrates.

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): NCT04797286


Contacts
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Contact: Stephen Mathai, MD 4106146311 smathai4@jhmi.edu
Contact: Dezeray Dutton 4435078222 dcephas1@jhu.edu

Locations
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United States, Louisiana
Louisiana State University Not yet recruiting
New Orleans, Louisiana, United States, 70806
Contact: Matthew Lammi, MD    504-568-4634      
Contact: Marie Sandi       mchild@lsuhsc.edu   
Principal Investigator: Matthew Lammi, MD         
United States, Maryland
Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Stephen Mathai, MD    410-614-6311    smathai4@jhmi.edu   
Contact: Dezeray Dutton    4435078222    dcephas1@jhu.edu   
Principal Investigator: Stephen Mathai, MD         
Sponsors and Collaborators
Johns Hopkins University
Louisiana State University Health Sciences Center in New Orleans
Investigators
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Principal Investigator: Stephen Mathai, MD Johns Hopkins University
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04797286    
Other Study ID Numbers: IRB00265164
First Posted: March 15, 2021    Key Record Dates
Last Update Posted: September 27, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Johns Hopkins University:
SSc-MEP
Additional relevant MeSH terms:
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Vascular Diseases
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Cardiovascular Diseases
Connective Tissue Diseases
Skin Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents