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Sildenafil for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS)

Primary Purpose

Scleroderma, Mildly Elevated Pulmonary Pressures

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Sildenafil

Placebo

About this trial

This is an interventional treatment trial for Scleroderma focused on measuring SSc-MEP

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Louisiana State University
Johns HopkinsRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sildenafil

Placebo

Arm Description

Sildenafil 20 mg by mouth three(3) times each day

Placebo by mouth three(3) times each day

Outcomes

Primary Outcome Measures

Difference in change in distance walked in 6 minute walk test (6MWT) at 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

Difference in change in distance walked in 6MWT at 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.

Difference in change in right ventricular function as assessed by cardiac MRI

As assessed by change in right ventricular function (normal/abnormal) on cardiac MRI.

Difference in change in right ventricular function as assessed by cardiac MRI

As assessed by change in right ventricular function (normal/abnormal) on cardiac MRI.

Difference in change in right ventricular function as assessed by invasive hemodynamics

As assessed by change in right ventricular function (normal/abnormal) on invasive hemodynamics.

Difference in change in right ventricular function as assessed by invasive hemodynamics

As assessed by change in right ventricular function (normal/abnormal) on invasive hemodynamics.

Difference in change in right ventricular function as assessed by echocardiography

As assessed by change in right ventricular function (normal/abnormal) on echocardiography.

Difference in change in right ventricular function as assessed by echocardiography

As assessed by change in right ventricular function (normal/abnormal) on echocardiography.

Difference in change in N-terminal pro b-type natriuretic peptide level

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.

Difference in change in health related quality of life as assessed by the 36-Item Short Form Health Survey (SF36) questionnaire

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.

Difference in change in health related quality of life as assessed by the emPHasis-10 health-related quality of life questionnaire (emPHasis-10).

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).

Difference in safety profile as assessed by frequency of adverse events

As assessed by frequency of adverse events between sildenafil and placebo groups.

Difference in safety profile as assessed by severity of adverse events

As assessed by severity of adverse events between sildenafil and placebo groups.

Full Information

NCT ID

NCT04797286

First Posted

March 11, 2021

Last Updated

September 12, 2023

Sponsor

Johns Hopkins University

Collaborators

Louisiana State University Health Sciences Center in New Orleans

1. Study Identification

Unique Protocol Identification Number

NCT04797286

Brief Title

Sildenafil for Early Pulmonary Vascular Disease in Scleroderma

Acronym

SEPVADIS

Official Title

Sildenafil for Early Pulmonary Vascular Disease in Scleroderma

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 20, 2021 (Actual)

Primary Completion Date

September 2024 (Anticipated)

Study Completion Date

September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Johns Hopkins University

Collaborators

Louisiana State University Health Sciences Center in New Orleans

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Scleroderma, Mildly Elevated Pulmonary Pressures

Keywords

SSc-MEP

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Sildenafil

Arm Type

Experimental

Arm Description

Sildenafil 20 mg by mouth three(3) times each day

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo by mouth three(3) times each day

Intervention Type

Drug

Intervention Name(s)

Sildenafil

Other Intervention Name(s)

Revatio, Viagra

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Oral pill placebo.

Primary Outcome Measure Information:

Title

Difference in change in distance walked in 6 minute walk test (6MWT) at 4 months

Description

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.

Time Frame

Baseline and 4 months

Secondary Outcome Measure Information:

Title

Difference in change in distance walked in 6MWT at 12 months

Description

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.

Time Frame

Baseline and 12 months

Title

Difference in change in right ventricular function as assessed by cardiac MRI

Description

As assessed by change in right ventricular function (normal/abnormal) on cardiac MRI.

Time Frame

Baseline and 4 months

Title

Difference in change in right ventricular function as assessed by cardiac MRI

Description

As assessed by change in right ventricular function (normal/abnormal) on cardiac MRI.

Time Frame

Baseline and 12 months

Title

Difference in change in right ventricular function as assessed by invasive hemodynamics

Description

As assessed by change in right ventricular function (normal/abnormal) on invasive hemodynamics.

Time Frame

Baseline and 4 months

Title

Difference in change in right ventricular function as assessed by invasive hemodynamics

Description

As assessed by change in right ventricular function (normal/abnormal) on invasive hemodynamics.

Time Frame

Baseline and 12 months

Title

Difference in change in right ventricular function as assessed by echocardiography

Description

As assessed by change in right ventricular function (normal/abnormal) on echocardiography.

Time Frame

Baseline and 4 months

Title

Difference in change in right ventricular function as assessed by echocardiography

Description

As assessed by change in right ventricular function (normal/abnormal) on echocardiography.

Time Frame

Baseline and 12 months

Title

Difference in change in N-terminal pro b-type natriuretic peptide level

Description

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.

Time Frame

Baseline, 4 months and 12 months

Title

Difference in change in health related quality of life as assessed by the 36-Item Short Form Health Survey (SF36) questionnaire

Description

Time Frame

Baseline, 4 months and 12 months

Title

Difference in change in health related quality of life as assessed by the emPHasis-10 health-related quality of life questionnaire (emPHasis-10).

Description

Time Frame

Baseline, 4 months and 12 months

Title

Difference in safety profile as assessed by frequency of adverse events

Description

As assessed by frequency of adverse events between sildenafil and placebo groups.

Time Frame

Ongoing until study closes, up to 4 years

Title

Difference in safety profile as assessed by severity of adverse events

Description

As assessed by severity of adverse events between sildenafil and placebo groups.

Time Frame

Ongoing until study closes, up to 4 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Stephen Mathai, MD

Phone

4106146311

smathai4@jhmi.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Dezeray Dutton

Phone

4435078222

dcephas1@jhu.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stephen Mathai, MD

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Louisiana State University

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70806

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Matthew Lammi, MD

Phone

504-568-4634

First Name & Middle Initial & Last Name & Degree

Marie Sandi

mchild@lsuhsc.edu

First Name & Middle Initial & Last Name & Degree

Matthew Lammi, MD

Facility Name

Johns Hopkins

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Stephen Mathai, MD

Phone

410-614-6311

smathai4@jhmi.edu

First Name & Middle Initial & Last Name & Degree

Dezeray Dutton

Phone

4435078222

dcephas1@jhu.edu

First Name & Middle Initial & Last Name & Degree

Stephen Mathai, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Sildenafil for Early Pulmonary Vascular Disease in Scleroderma

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