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

• ClinicalTrials.gov Identifier: NCT00077584
• Recruitment Status: Completed
• First Posted: February 11, 2004
• Last Update Posted: October 27, 2016
• Sponsor: Actelion
• Information provided by (Responsible Party): Actelion

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Digital Ulcers; Systemic Sclerosis	Drug: Bosentan 62.5 mg; Drug: Bosentan 125 mg; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 188 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: October 2003
• Actual Primary Completion Date: March 2005
• Actual Study Completion Date: May 2005

Arms and Interventions

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 Name: Ro 47-0203; Drug: Bosentan 125 mg; Oral tablets containing 125 mg of bosentan; Other Name: 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

Outcome Measures

Primary Outcome Measures :

1. Time to complete healing of the cardinal ulcer (CU) up to Week 24 in patients with CU healing maintained for 12 weeks [ Time Frame: 24 weeks ]
2. Total number of new digital ulcers per patient up to Week 24 [ Time Frame: 24 weeks ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

Barri Fessler, MD

Birmingham, Alabama, United States, 35249-7201

United States, California

Daniel Furst, MD

Los Angeles, California, United States, 90095-1670

United States, Colorado

David Collier, MD

Aurora, Colorado, United States, 80010

United States, Connecticut

Naomi Rothfield, MD

Farmington, Connecticut, United States, 06030-1310

United States, Illinois

Michael Ellman, MD

Chicago, Illinois, United States, 60637

United States, Louisiana

Mittie Doyle, MD

New Orleans, Louisiana, United States, 70112

United States, Maryland

Frederick Wigley, MD

Baltimore, Maryland, United States, 21224

United States, Massachusetts

Joseph Korn, MD

Boston, Massachusetts, United States, 02118-2394

United States, Michigan

Richard Martin, MD

Grand Rapids, Michigan, United States, 49503

United States, Minnesota

Thomas Osborn, MD

Rochester, Minnesota, United States, 55905

United States, New Jersey

Vivien Hsu, MD

New Brunswick, New Jersey, United States, 08903

United States, New York

Lee Shapiro, MD

Albany, New York, United States, 12206

Avram Goldberg, MD

Manhasset, New York, United States, 11030

United States, Ohio

Bashar Kahaleh, MD

Toledo, Ohio, United States, 43614

United States, Pennsylvania

Chris Derk, MD

Philadelphia, Pennsylvania, United States, 19107

Thomas Medsger, MD

Pittsburgh, Pennsylvania, United States, 15261

United States, South Carolina

Edwin Smith, MD

Charleston, South Carolina, United States, 29425

United States, Texas

Maureen Mayes, MD

Houston, Texas, United States, 77030

United States, Washington

Jerry Molitor, MD

Seattle, Washington, United States, 98101

Howard Kenney, MD

Spokane, Washington, United States, 99204

United States, Wisconsin

Mary Ellen Csuka, MD

Milwaukee, Wisconsin, United States, 53211

Canada, Ontario

Janet Pope, MD

London, Ontario, Canada, N6A 4V2

Peter Lee, MD

Toronto, Ontario, Canada, M5G 1X5

Canada, Quebec

Eric Rich, MD

Montreal, Quebec, Canada, H2L 4M1

Murray Baron, MD

Montreal, Quebec, Canada, H3T1E2

Sponsors and Collaborators

Actelion

Investigators

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

More Information

Publications of Results:

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.

• Responsible Party: Actelion
• ClinicalTrials.gov Identifier: NCT00077584
• Obsolete Identifiers: NCT02800993
• Other Study ID Numbers: AC-052-331
• First Posted: February 11, 2004
• Last Update Posted: October 27, 2016
• Last Verified: October 2016

Keywords provided by Actelion:

Scleroderma; Finger Ulcers; Digital Ulcers; Systemic Sclerosis

Additional relevant MeSH terms:

Scleroderma, Systemic; Scleroderma, Diffuse; Skin Ulcer; Sclerosis; Ulcer; Pathologic Processes; Connective Tissue Diseases; Skin Diseases; Bosentan; Antihypertensive Agents; Endothelin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action