Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial

Matthew R Lammi; Monica Mukherjee; Lesley Ann Saketkoo; Kyle Carey; Laura Hummers; Steven Hsu; Amita Krishnan; Marie Sandi; Ami A Shah; Stefan L Zimmerman; Paul M Hassoun; Steven C Mathai

doi:10.1186/s12890-024-02892-3

Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial

BMC Pulm Med. 2024 Apr 30;24(1):211. doi: 10.1186/s12890-024-02892-3.

Authors

Matthew R Lammi^{1

2

3

4}, Monica Mukherjee⁵, Lesley Ann Saketkoo^{6

7}, Kyle Carey⁸, Laura Hummers⁹, Steven Hsu⁵, Amita Krishnan^{10

11}, Marie Sandi¹⁰, Ami A Shah⁹, Stefan L Zimmerman¹², Paul M Hassoun¹³, Steven C Mathai¹³

Affiliations

¹ Louisiana State University Health Sciences, 1901 Perdido St, 70112, New Orleans, LA,, USA. [email protected].
² Comprehensive Pulmonary Hypertension Center, University Medical Center, New Orleans, USA. [email protected].
³ New Orleans Scleroderma and Sarcoidosis Patient Care and Research Center, New Orleans, USA. [email protected].
⁴ Johns Hopkins University, Division of Pulmonary and Critical Care Medicine, Baltimore, USA. [email protected].
⁵ Division of Cardiology, Johns Hopkins University, Baltimore, USA.
⁶ New Orleans Scleroderma and Sarcoidosis Patient Care and Research Center, New Orleans, USA.
⁷ Tulane University School of Medicine, New Orleans, USA.
⁸ Institute for Clinical and Translational Medicine, Johns Hopkins University, Baltimore, USA.
⁹ Johns Hopkins University, Division of Rheumatology, Baltimore, USA.
¹⁰ Louisiana State University Health Sciences, 1901 Perdido St, 70112, New Orleans, LA,, USA.
¹¹ Comprehensive Pulmonary Hypertension Center, University Medical Center, New Orleans, USA.
¹² Johns Hopkins University, Department of Radiology and Radiological Science, Baltimore, USA.
¹³ Johns Hopkins University, Division of Pulmonary and Critical Care Medicine, Baltimore, USA.

Abstract

Background: Pulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc). An important component of SSc patient management is early detection and treatment of PH. Recently the threshold for the diagnosis of PH has been lowered to a mean pulmonary artery pressure (mPAP) threshold of > 20 mmHg on right heart catheterization (RHC). However, it is unknown if PH-specific therapy is beneficial in SSc patients with mildly elevated pressure (SSc-MEP, mPAP 21-24 mmHg).

Methods: The SEPVADIS trial is a randomized, double-blind, placebo-controlled phase 2 trial of sildenafil in SSc-MEP patients with a target enrollment of 30 patients from two academic sites in the United States. The primary outcome is change in six-minute walk distance after 16 weeks of treatment. Secondary endpoints include change in pulmonary arterial compliance by RHC and right ventricular function by cardiac magnetic resonance imaging at 16 weeks. Echocardiography, serum N-terminal probrain natriuretic peptide, and health-related quality of life is being measured at 16 and 52 weeks.

Discussion: The SEPVADIS trial will be the first randomized study of sildenafil in SSc-MEP patients. The results of this trial will be used to inform a phase 3 study to investigate the efficacy of treating patients with mild elevations in mPAP.

Trial registration: ClinicalTrials.gov Identifier NCT04797286.

Keywords: Clinical trial; Pulmonary hypertension; Scleroderma; Sildenafil; Systemic sclerosis.

Publication types

Clinical Trial Protocol

MeSH terms

Adult
Cardiac Catheterization
Clinical Trials, Phase II as Topic
Double-Blind Method
Echocardiography
Female
Humans
Hypertension, Pulmonary* / drug therapy
Hypertension, Pulmonary* / etiology
Male
Middle Aged
Natriuretic Peptide, Brain / blood
Peptide Fragments / blood
Pulmonary Artery
Quality of Life*
Randomized Controlled Trials as Topic
Scleroderma, Systemic* / complications
Scleroderma, Systemic* / drug therapy
Sildenafil Citrate* / therapeutic use
Treatment Outcome
Vasodilator Agents / therapeutic use
Walk Test

Substances

pro-brain natriuretic peptide (1-76)

Associated data

ClinicalTrials.gov/NCT04797286