A Randomized Control Trial to Assess the Efficacy of Tadalafil in Raynaud's Phenomenon in Scleroderma

A Randomized Control Trial to Assess the Efficacy of Tadalafil in Raynaud's Phenomenon in Scleroderma: A Double Blind, Parallel Group, Multicentric Study

Raynaud's phenomenon (RP) associated with scleroderma is a difficult problem to treat. Many patients develop ischemic digital ulcers due to severe RP that causes considerable morbidity and adversely affects the quality of life. In an earlier study, we have observed marked improvement in RP attacks and rapid healing of digital ulcers following therapy with phosphodiesterase V inhibitor, Tadalafil. In the present multicentric study we aim to study the efficacy of Tadalafil in patients continuing to have RP attacks despite using at least one or more vasodilators.

Study Overview

• Status: Completed
• Conditions: Scleroderma; Raynaud's Phenomenon; Digital Ulcers
• Intervention / Treatment: Drug: Tadalafil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • ND
    • New Delhi, ND, India
      • Department of Clinical Immunology, Army R&R hospital
  • Punjab
    • Chandigarh, Punjab, India
      • Medicine Unit II, PGIMER
  • UP
    • Lucknow, UP, India, 226014
      • Department of Immunology, SGPGIMS
  • WB
    • Kolkatta, WB, India
      • Immunology Rheumatology Unit, IPGMER

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Male or female subjects between the ages of 18 years and 65 years will be selected for the study if they have a clinical diagnosis of Raynaud's phenomenon secondary to systemic sclerosis (scleroderma) despite being on vasodilator therapy. Raynaud's phenomenon is defined as a history of cold sensitivity associated with colour changes of cyanosis or pallor. Patients with a history of at least 4 attacks per week during two-week pre-trial period even with treatment with other vasodilators will be recruited. Patients fulfilling the diagnostic criteria of scleroderma (as per American College of Rheumatology criteria) or having presence of at least 3 of the 5 features of the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias)will be invited to participate in the study.

Exclusion Criteria:

Patients with:

• Symptomatic orthostatic hypotension,
• Evidence of current malignancy,
• History of sympathectomy,
• Upper extremity deep vein thrombosis or lymphedema within 3 months,
• Recent surgical procedure requiring general anesthesia,
• Acute Myocardial Infarction, unstable angina, strokes and transient ischemic attacks within the past three months,
• Smoking,
• Use of any investigational drug within 30 days of the study sessions,
• Use of medications that might interfere with tadalafil like nitrates and alpha adrenergic blockers that have vasoactive effects, and patients taking potent inhibitors of CYP3A4 such as ritonavir, ketoconazole, and itraconazole, erythromycin, itraconazole, and grapefruit juice,
• Patients taking alcohol,
• Patients with bleeding disorders
• Significant active peptic ulceration,
• Current pregnancy,
• Current breast-feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Tab Placebo every alternate day for 8 weeks
EXPERIMENTAL: Tadalafil	Drug: Tadalafil; Tab Tadalafil, 20 mg alternate day for 8 weeks; Other Names: Tadalis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Daily frequency, duration and severity of Raynaud's phenomenon	Baseline and 8 weeks
Appearance or healing of digital ulcers	Baseline and 8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Improvement in health assessment questionnaire	Baseline and 8 weeks
Improvement in scleroderma specific health assessment questionnaire	Baseline and 8 weeks
Improvement in quality of life	Baseline and 8 weeks
Improvement in biomarkers of endothelial dysfunction	Baseline and 8 weeks
Improvement in flow mediated dilatation	Baseline and 8 weeks

Collaborators and Investigators

• Sponsor: Sanjay Gandhi Postgraduate Institute of Medical Sciences
• Collaborators: Postgraduate Institute of Medical Education and Research; Institute of Postgraduate Medical Education and Research; Army Research and Referral hospital
• Investigators: Principal Investigator: Parasar Ghosh, MD, DM, IPGMER, Kolkatta; Principal Investigator: Aman Sharma, MD, PGIMER, Chandigarh; Principal Investigator: Darshan S Bhakuni, MD, Army R&R Hospital, New Delhi

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (ACTUAL): April 1, 2010
• Study Completion (ACTUAL): May 1, 2010

Study Registration Dates

• First Submitted: May 3, 2010
• First Submitted That Met QC Criteria: May 3, 2010
• First Posted (ESTIMATE): May 5, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): May 10, 2010
• Last Update Submitted That Met QC Criteria: May 7, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: endothelial dysfunction; scleroderma; digital ulcers; ischemic ulcers; Raynaud's phenomenon; gangrene; vasodilators; digital infarcts
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Connective Tissue Diseases; Peripheral Vascular Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Scleroderma, Localized; Raynaud Disease; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Tadalafil
• Other Study ID Numbers: B22:A15:PGI/DM/EC/40/7.11.2007