Efficacy and Safety of Oral Bosentan on Healing/Prevention of Digital (Finger) Ulcers in Patients With Scleroderma (RAPIDS-2)

A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Effect of Bosentan on Healing and Prevention of Ischemic Digital Ulcers in Patients With Systemic Sclerosis

In an earlier clinical trial, RAPIDS-1, conducted in scleroderma patients with or without digital ulcers at baseline, bosentan significantly reduced the number of new digital ulcers versus placebo. The purpose of the present trial (RAPIDS-2) is to evaluate the prevention and healing effects of bosentan versus placebo on digital ulcers over a 24-week treatment period.

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis; Digital Ulcers
• Intervention / Treatment: Drug: Bosentan 62.5 mg; Drug: Bosentan 125 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4V2
      • Janet Pope, MD
    • Toronto, Ontario, Canada, M5G 1X5
      • Peter Lee, MD
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Eric Rich, MD
    • Montreal, Quebec, Canada, H3T1E2
      • Murray Baron, MD
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249-7201
      • Barri Fessler, MD
  • California
    • Los Angeles, California, United States, 90095-1670
      • Daniel Furst, MD
  • Colorado
    • Aurora, Colorado, United States, 80010
      • David Collier, MD
  • Connecticut
    • Farmington, Connecticut, United States, 06030-1310
      • Naomi Rothfield, MD
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Michael Ellman, MD
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Mittie Doyle, MD
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Frederick Wigley, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02118-2394
      • Joseph Korn, MD
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Richard Martin, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Thomas Osborn, MD
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Vivien Hsu, MD
  • New York
    • Albany, New York, United States, 12206
      • Lee Shapiro, MD
    • Manhasset, New York, United States, 11030
      • Avram Goldberg, MD
  • Ohio
    • Toledo, Ohio, United States, 43614
      • Bashar Kahaleh, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Chris Derk, MD
    • Pittsburgh, Pennsylvania, United States, 15261
      • Thomas Medsger, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Edwin Smith, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Maureen Mayes, MD
  • Washington
    • Seattle, Washington, United States, 98101
      • Jerry Molitor, MD
    • Spokane, Washington, United States, 99204
      • Howard Kenney, MD
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53211
      • Mary Ellen Csuka, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

• Systemic Sclerosis (SSc), diffuse or limited.
• SSc patients with at least one digital ulcer at baseline qualifying as a cardinal ulcer.

Main Exclusion Criteria:

• Digital ulcers due to conditions other than SSc.
• Severe pulmonary arterial hypertension (PAH) (Who class III and IV).
• Malabsorption or any severe organ failure (e.g., lung, kidney, liver) or any life-threatening condition.
• Treatment with parenteral prostanoids (prostaglandin E, epoprostenol, or prostacyclin analogs) during the past 3 months prior to randomization.
• Treatment with inhaled or oral prostanoids one month prior to randomization.
• Previous treatment with bosentan.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bosentan; The patients received bosentan 62.5 mg twice daily (b.i.d.) for 4 weeks and then 125 mg b.i.d. for 20 weeks	Drug: Bosentan 62.5 mg; Oral tablets containing 62.5 mg of bosentan; Other Names: Ro 47-0203; Drug: Bosentan 125 mg; Oral tablets containing 125 mg of bosentan; Other Names: Ro 47-0203
Placebo Comparator: Placebo; The patients received the matching placebo for 24 weeks	Drug: Placebo; Oral tablets matching bosentan 62.5-mg tablets and bosentan 125-mg tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to complete healing of the cardinal ulcer (CU) up to Week 24 in patients with CU healing maintained for 12 weeks	24 weeks
Total number of new digital ulcers per patient up to Week 24	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to Week 24 in hand pain	Pain assessed on visual analog scales	Baseline and Week 24
Change from baseline to Week 24 in hand disability	Hand disability indexed assessed using the Health Assessment Questionaire (HAQ)	Baseline and Week 24
Proportion of subjects with treatment-emergent adverse events		up to 32 weeks (8 week post-treatment follow-up)
Proportion of subjects with liver function abnormalities	Increase in aminotransferases	Every 4 weeks up to Week 24

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Principal Investigator: James Seibold, MD, Robert Wood Johnson Medical School, New Brunswick, NJ, USA

Publications and helpful links

General Publications

• Matucci-Cerinic M, Denton CP, Furst DE, Mayes MD, Hsu VM, Carpentier P, Wigley FM, Black CM, Fessler BJ, Merkel PA, Pope JE, Sweiss NJ, Doyle MK, Hellmich B, Medsger TA Jr, Morganti A, Kramer F, Korn JH, Seibold JR. Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2011 Jan;70(1):32-8. doi: 10.1136/ard.2010.130658. Epub 2010 Aug 30.
• Liu C, Chen J, Gao Y, Deng B, Liu K. Endothelin receptor antagonists for pulmonary arterial hypertension. Cochrane Database Syst Rev. 2021 Mar 26;3(3):CD004434. doi: 10.1002/14651858.CD004434.pub6.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): March 1, 2005
• Study Completion (Actual): May 1, 2005

Study Registration Dates

• First Submitted: February 10, 2004
• First Submitted That Met QC Criteria: February 10, 2004
• First Posted (Estimated): February 11, 2004

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Systemic Sclerosis; Scleroderma; Digital Ulcers; Finger Ulcers
• Additional Relevant MeSH Terms: Pathologic Processes; Connective Tissue Diseases; Skin Diseases; Sclerosis; Ulcer; Scleroderma, Systemic; Scleroderma, Diffuse; Skin Ulcer; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; Bosentan
• Other Study ID Numbers: AC-052-331