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Trial record 101 of 671 for:    Recruiting, Not yet recruiting, Available Studies | "Antihypertensive Agents"

Assess Efficacy of of Oral Treprostinil in Patients With Symptomatic Primary or Secondary Raynaud's Phenomenon

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ClinicalTrials.gov Identifier: NCT02583789
Recruitment Status : Recruiting
First Posted : October 22, 2015
Last Update Posted : August 2, 2017
Sponsor:
Collaborator:
United Therapeutics
Information provided by (Responsible Party):
Aaron Waxman MD PhD, Brigham and Women's Hospital

Brief Summary:

This study represents the first trial to assess the efficacy of oral treprostinil therapy in patients with symptomatic primary or secondary Raynaud's Phenomenon (RP) resistant to vasodilatory therapy.

The study will be randomized 1:1 UT-15C to placebo. The design is a crossover study and all subjects will be randomized to receive oral treprostinil sustained release tablets or matching placebo for 12 weeks and then crossover for 12 weeks. All subjects will be exposed for 12 weeks of treatment with oral UT-15C during the study.


Condition or disease Intervention/treatment Phase
Raynaud's Phenomenon Drug: oral treprostinil Drug: Placebo Early Phase 1

Detailed Description:

A single center double-blinded, placebo-controlled, crossover study to assess efficacy of oral treprostinil titrated to a tolerable goal dose of 2.0 mg three times per day (TID) in 20 patients with symptomatic primary or secondary Raynaud's Phenomenon resistant to vasodilatory therapy. Based on a pre-screening survey of the clinic population we anticipate at least 30 patients per year will be eligible for enrollment. At the clinicians discretion the dose can be increased as tolerated.

Eligible subjects at the time of signing an informed consent will have a diagnosis of primary or secondary Raynaud's Phenomenon. Subjects will be recruited from the Raynaud's Clinic, which is a multidisciplinary clinic held at the Watkins Clinic at the Shapiro Cardiovascular Center. Subjects will be assessed during a Screening and treatment initiation visit to determine eligibility for the study.

This study represents the first trial to assess the efficacy of oral treprostinil therapy in patients with symptomatic primary or secondary Raynaud's phenomenon resistant to vasodilatory therapy.

Oral treprostinil (UT-15C), a synthetic prostacyclin analog that inhibits platelet aggregation, induces vasodilation, and suppresses smooth muscle proliferation. In a recent open label study of escalating doses of oral treprostinil in patients with systemic sclerosis and digital ischemia, oral treprostinil was effectively absorbed in patients with scleroderma and was temporally associated with improved cutaneous perfusion and temperature. Thus, oral treprostinil may provide a new therapeutic option for patients with refractory secondary Raynaud's Phenomenon.

A recent systematic review demonstrated that oral calcium channel blockers, the most commonly prescribed drugs for primary RP, are only minimally effective in reducing the frequency of attacks and severity. Although Sildenafil has been shown to increase digital skin blood flow during all phases of local cooling in primary RP, its role in primary RP is not yet confirmed in randomized, controlled trials. To our knowledge, very few studies have assessed the use of oral prostacyclin therapy for disabling primary RP, although one multicenter, double-blind, randomized trial of an oral analog of prostacyclin, known as beraprost, reduced the number of RP attacks but proved no more beneficial than placebo.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blinded, Placebo-controlled, Crossover Study to Assess Efficacy of Oral Treprostinil Titrated to Highest Tolerable Dose in 20 Patients With Symptomatic Primary or Secondary Raynaud's Phenomenon Resistant to Vasodilatory Therapy
Study Start Date : May 2016
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: oral treprostinil
Dosing of oral treprostinil will be initiated at 0.125 mg three times daily. Dose escalations of oral treprostinil can occur every 72 hours (three consecutive doses) in 0.125 mg increments. Subjects will be titrated as tolerated to a goal dose of 2mg TID over a 6-week period.
Drug: oral treprostinil
Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase
Other Name: Orenitram

Drug: Placebo
Placebo is a sugar pill manufactured to resemble UT-15C. Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase
Other Name: Sugar pill

Placebo Comparator: Placebo
Placebo mimics oral treprostinil and will be taken three times a day
Drug: oral treprostinil
Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase
Other Name: Orenitram

Drug: Placebo
Placebo is a sugar pill manufactured to resemble UT-15C. Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase
Other Name: Sugar pill




Primary Outcome Measures :
  1. Change in Raynaud's Condition Score [ Time Frame: from baseline (2-week run in) to 6 weeks of treatment ]
    Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase


Secondary Outcome Measures :
  1. Change in number of Raynaud's Phenomenon attacks [ Time Frame: from baseline (2-week run in) to 6 weeks of treatment ]
    Change in the number of Raynaud's Phenomenon attacks per week during the sixth week of treatment phase compared to the number of Raynaud's Phenomenon attacks per week at baseline.

  2. Change in duration of Raynaud's Phenomenon attacks [ Time Frame: from baseline (2-week run in) to 6 weeks of treatment ]
    Change in the total duration of Raynaud's Phenomenon attacks per week during the sixth week of treatment compared to the total duration of Raynaud's Phenomenon attacks per week at baseline.

  3. Reduction of ulcer burden among secondary Raynaud's Phenomenon patients [ Time Frame: from baseline (2-week run in) to 6 weeks of treatment ]
    Decrease ulcer burden in secondary Raynaud's Phenomenon patients by reducing the time to heal active ulcers and/or reducing the number of new ulcers.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged ≥18-65 years
  • Active Raynaud's Phenomenon defined as patients with refractory RP having four or more RP attacks per week in the 2 weeks before inclusion in the study despite treatment with vasodilators for at least 3 months
  • Patients with primary Raynaud's Phenomenon
  • Patients with Raynaud's secondary to connective tissue diseases (including scleroderma (SSc), limited scleroderma (CREST), mixed connective tissue disease (MCTD), primary Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), with diagnosis of the underlying rheumatic disease based on standard criteria
  • Patients on stable dose phosphodiesterase inhibitors (sildenafil, tadalafil or vardenafil), endothelin antagonists, alpha adrenergic antagonists, or calcium channel blockers defined as 3-months with no change in dose will be allowed to participate

Exclusion Criteria:

  • Uncontrolled hypertension, diabetes mellitus, history of orthostatic hypotension, acute coronary or cerebrovascular event within 3 months, evidence of malignancy, history of sympathectomy
  • Smoking within 3 months or smoking cessation using nicotine products
  • Subjects currently taking or other prostacyclins.
  • Pregnant or breast feeding or considering pregnancy in next 4 months
  • Participation in trial with an investigational drug within 30 days

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02583789


Contacts
Contact: Laurie Lawler, RN 617-525-9731 llawler@partners.org
Contact: Sergio Segrera ssegrera@partners.org

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Laurie Lawler, RN    617-525-9731    llawler@partners.org   
Contact: Sergio Segrera       ssegrera@partners.org   
Principal Investigator: Aaron Waxman, MD, PhD         
Principal Investigator: Paul Dellaripa, MD         
Sponsors and Collaborators
Brigham and Women's Hospital
United Therapeutics
Investigators
Principal Investigator: Aaron Waxman, MD/PhD Brigham and Womens Hospital
Principal Investigator: Paul Dellaripa, MD Brigham and Womens Hospital