Sildenafil Effect on Digital Ulcer Healing in sClerodErma SEDUCE STUDY

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Lille
ClinicalTrials.gov Identifier:
NCT01295736
First received: February 11, 2011
Last updated: January 31, 2014
Last verified: July 2012
  Purpose

Digital ulcers (DUs) are an expression of the microangiopathy in patients with scleroderma (SSc). DUs lead to pain and impaired hand use. DUs remain a severe complication for many patients and effective therapy remains elusive. In the present study, the investigators propose to evaluate the efficacy of Sildenafil in DUs healing in a randomized double blind control study in SSc patients.


Condition Intervention Phase
Systemic Scleroderma
Drug: Sildenafil
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation of the Efficacy of Sildenafil on Time to Healing in Patients With Scleroderma and Ischaemic Digital Ulcers: a Prospective, Longitudinal, Randomized, Comparative, Double-blind, 2-parallel-arm, Placebo-controlled Study

Resource links provided by NLM:


Further study details as provided by University Hospital, Lille:

Primary Outcome Measures:
  • time to healing of ischemic digital ulcers (DUs) in patients with scleroderma treated by sildenafil 20 mg TID versus placebo for 90 days [ Time Frame: 90 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the time to healing of ischemic DUs (2 mm at entry and > 1 month and <3 months old) in patients with scleroderma treated by sildenafil 20 mg TID versus placebo for 90 days. [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • To evaluate the change in the number of ischaemic DUs between baseline and day 90. [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • To evaluate the proportion of patients with complete healing of all DUs present at baseline at day 90. [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • To evaluate the proportion of patients with complete healing of all DUs (baseline DUs and new DUs) at day 90. [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • To evaluate the proportion of patients who do not develop any new DU after 28 days of treatment with the study drug up to day 90. [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • To evaluate the change between baseline and day 90 in hand function and pain. [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • To evaluate the proportion of patients with complicated DUs (infection, gangrene, amputation, DU requiring IV prostanoids) over the 90 days period of treatment. [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • To evaluate the evolution of the severity of Raynaud's phenomenon between baseline and day 90. [ Time Frame: 90 days ] [ Designated as safety issue: No ]

Enrollment: 84
Study Start Date: November 2010
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Actif arm
Sildenafil 20mg TID during 90 days
Drug: Sildenafil
Sildenafil 20 mg TID per os during 90 days
Placebo Comparator: Sugar pill
Placebo pills TID during 90 days
Drug: placebo
Placebo pills TID per os during 90 days

Detailed Description:

This is a multicenter, prospective, longitudinal, randomized, comparative, double-blind, 2-parallel-arm, placebo-controlled study aimed to evaluate the efficacy of sildenafil 20 mg TID study on time to healing of DUs in SSc patients with ischaemic DUs.

Approximately 120 patients aged from 18 years and above will be allocated to receive either placebo or sildenafil 20mg TID during 90 days. All potential subjects will present with ischaemic digital ulcers complicating scleroderma. An eligible digital ulcer must be beyond the proximal interphalangeal joint, on finger surface (included periungual ulcers), of ischemic origin according to the physician, and not over subcutaneous calcifications or bone relief.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient with systemic sclerosis (ScS) according to the classification criteria of the American College of Rheumatology or of "LeRoy" and "Medsger".
  • ScS patient with at least one ongoing ischaemic hand digital ulcer at baseline (see below the eligibility conditions of a digital ulcer).
  • Patient must have provided written informed consent prior to enrolment. Patient agrees to come to the follow up visits inside the protocol specified range.
  • Relative to each DU: DU must be beyond the proximal interphalangeal joint, on finger surface, of ischemic origin according to the physician, and not over subcutaneous calcifications or bone relief.

Exclusion Criteria:

  • PAH requiring PDE5 inhibitors or prostacyclin history of stroke, myocardial infarction or life threatening arrhythmia within the last 6 months
  • severe cardiac failure (NYHA IV) or unstable angina within the last 6 months.
  • hereditary degenerative retinal disorders non-arteritic anterior ischemic optic neuropathy or untreated proliferative diabetic retinopathy
  • uncontrolled diabetes mellitus
  • Patient with known severe lung obstructive disease (FEV1<70% on last available pulmonary function tests).
  • severe hepatic impairment
  • Patient with known impairment of renal function (serum creatinine > 2.5 ULN).
  • Patient with severe malabsorption or any severe organ failure (e.g., lung, kidney) or any life-threatening condition.
  • Patient who has had surgical sympathectomy performed in the previous 12 months.
  • Patient with a history of upper extremity deep vein thrombosis or lymphedema within the previous 3 months.
  • Patient participating in a clinical trial or having participated in a clinical trial within the previous 3 months.
  • Patient having received a treatment with sildenafil for digital ulcers or pulmonary arterial hypertension within 3 months prior to inclusion.
  • Patient having received a treatment with parenteral prostanoids (prostaglandin E, epoprostenol, treprostinil sodium or other prostacyclin analogs) within 3 months prior to inclusion.
  • Patient having received a treatment with inhaled or oral prostanoids one month prior to inclusion.
  • Patient with previous intolerance or allergy to PDE5 inhibitors or a history of multiple clinically significant allergies.
  • Pregnant or lactating female.
  • Patient with uncontrolled tachyarrhythmias or bradyarrhythmias, or placement of pacemaker or implantable defibrillator within 60 days prior to randomization.
  • Patient with hemodynamic instability or systolic arterial pressure less than 90 mmHg and/or symptomatic orthostatic hypotension.
  • Patient receiving all forms of prostacyclin or nitrates or nitric oxide donors in any form including Nicorandil.
  • Patient receiving potent inhibitors of CYP3A4 such as ketoconazole, itraconazole, ritonavir.
  • Patient with any condition that prevents compliance with the protocol or adhering to therapy.
  • Patient who has donated blood during the previous month or intends to donate blood or blood products during the study or for one month following completion of the study.
  • Patient under guardianship (including curators) or deprived of liberty.
  • Patient presenting with an anatomic malformation of penis (such as an angulation, sclerosis of erectile tissue or "Lapeyronie's disease").
  • Patient presenting with a disease which predisposes to priapism (such as sickle-cell disease, myeloma or leukemia).
  • Patient presenting with at least one digital ulcer meeting the exclusion criteria (see below).
  • Relative to each DU:
  • Digital ulcer due to conditions other than scleroderma.
  • Non ischaemic digital ulcer.
  • Infected digital ulcer requiring systemic antibiotherapy.
  • Digital ulcer requiring urgent surgery.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01295736

Locations
France
University Hospital, Nice
Nice, Alpes-Maritimes, France, 06000
Hautepierre Hospital
Strasbourg, Bas-Rhin, France, 67098
Nord Hospital
Marseille, Bouches du Rhone, France, 13915
CHU de Caen
Caen, Calvados, France, 14033
CHU Dijon
Dijon, Côte d'Or, France, 21000
CHU Dupuytren / Médecine Interne
Limoges, Haute Vienne, France, 87042
CHU Dupuytren / dermatology
Limoges, Haute Vienne, France, 87042
Jean Verdier Hospital
Bondy, Ile de France, France, 93130
La Pitié - Salpétriêre Hospital
Paris, Ile de France, France, 75013
Saint Antoine Hospital
Paris, Ile de France, France, 75571
Cochin Hospital / Médecine Interne
Paris, Ile de France, France, 75014
Groupe Hospitalier Paris Saint Joseph
Paris, Ile de France, France, 75674
Cochin Hospital
Paris, Ile de France, France, 75014
CHU de Rennes
Rennes, Ile et Vilaine, France, 35203
University Hospital, Tours
Tours, Indre-et-Loire, France, 37000
University Hospital, Grenoble
Grenoble, Isère, France, 38043
University Hospital, Nantes
Nantes, Loire-Atlantique, France, 44000
CHU de Reims
Reims, Marne, France, 51092
University Hospital, Fort de France
Fort de France, Martinique, France, 97 261
University Hospital, Lille
Lille, Nord, France, 59037
University Hospital, Rouen
Rouen, Seine-Maritime, France, 76000
University Hospital, Amiens
Amiens, Somme, France, 80000
Hôpital Edouard Herriot
Lyon, France, 69437
St Louis Hospital
Paris, France, 75010
Sponsors and Collaborators
University Hospital, Lille
Investigators
Principal Investigator: Eric HACHULLA, PU-PH University Hospital, Lille
  More Information

No publications provided

Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT01295736     History of Changes
Other Study ID Numbers: 2010-021135-13, 2010_14
Study First Received: February 11, 2011
Last Updated: January 31, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Lille:
scleroderma
digital
ulcer

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Ulcer
Connective Tissue Diseases
Skin Diseases
Pathologic Processes
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on August 26, 2014