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

NCT01117298 | Completed Phase 3

• 1 other identifier: B22:A15:PGI/DM/EC/40/7.11.2007
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Raynaud's Phenomenon; Digital Ulcers; Scleroderma

Keywords

Raynaud's phenomenon; ischemic ulcers; digital ulcers; digital infarcts; gangrene; vasodilators; endothelial dysfunction; scleroderma

Outcome Measures

Primary Outcomes (2)

• Daily frequency, duration and severity of Raynaud's phenomenon

  Baseline and 8 weeks

• Appearance or healing of digital ulcers

  Baseline and 8 weeks

Secondary Outcomes (5)

• 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

Study Arms (2)

Tadalafil

EXPERIMENTAL

Drug: Tadalafil

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tadalafil DRUG

Tab Tadalafil, 20 mg alternate day for 8 weeks

Also known as: Tadalis

Tadalafil

Placebo DRUG

Tab Placebo every alternate day for 8 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanjay Gandhi Postgraduate Institute of Medical Sciences: lead
• Institute of Postgraduate Medical Education and Research: collaborator
• Post Graduate Institute of Medical Education and Research, Chandigarh: collaborator
• Army Hospital Research And Referral, India: collaborator

Study Sites (4)

Department of Clinical Immunology, Army R&R hospital

New Delhi, ND, India

Location

Medicine Unit II, PGIMER

Chandigarh, Punjab, India

Location

Department of Immunology, SGPGIMS

Lucknow, Uttar Pradesh, 226014, India

Location

Immunology Rheumatology Unit, IPGMER

Kolkata, West Bengal, India

Location

Related Publications (1)

• Maltez N, Maxwell LJ, Rirash F, Tanjong Ghogomu E, Harding SE, Tingey PC, Wells GA, Tugwell P, Pope J. Phosphodiesterase 5 inhibitors (PDE5i) for the treatment of Raynaud's phenomenon. Cochrane Database Syst Rev. 2023 Nov 6;11(11):CD014089. doi: 10.1002/14651858.CD014089.

  PMID: 37929840 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Raynaud Disease; digital ulcers; Scleroderma, Diffuse; Gangrene

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Scleroderma, Systemic; Connective Tissue Diseases; Necrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: May 3, 2010
• First Posted: May 5, 2010
• Study Start: November 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: May 1, 2010
• Last Updated: May 10, 2010

Record last verified: 2010-05

Locations

IN (4)