Assess Efficacy of of Oral Treprostinil in Patients With Symptomatic Primary or Secondary Raynaud's Phenomenon
Primary Purpose
Raynaud's Phenomenon
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
oral treprostinil
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Raynaud's Phenomenon
Eligibility 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
Sites / Locations
- Brigham and Women's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
oral treprostinil
Placebo
Arm Description
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.
Placebo mimics oral treprostinil and will be taken three times a day
Outcomes
Primary Outcome Measures
Change in Raynaud's Condition Score
Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase
Secondary Outcome Measures
Change in number of Raynaud's Phenomenon attacks
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.
Change in duration of Raynaud's Phenomenon attacks
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.
Reduction of ulcer burden among secondary Raynaud's Phenomenon patients
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.
Full Information
NCT ID
NCT02583789
First Posted
October 8, 2015
Last Updated
January 5, 2022
Sponsor
Brigham and Women's Hospital
Collaborators
United Therapeutics
1. Study Identification
Unique Protocol Identification Number
NCT02583789
Brief Title
Assess Efficacy of of Oral Treprostinil in Patients With Symptomatic Primary or Secondary Raynaud's Phenomenon
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 Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Completed
Study Start Date
May 2016 (undefined)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
December 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
United Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Raynaud's Phenomenon
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
oral treprostinil
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo mimics oral treprostinil and will be taken three times a day
Intervention Type
Drug
Intervention Name(s)
oral treprostinil
Other Intervention Name(s)
Orenitram
Intervention Description
Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar pill
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in Raynaud's Condition Score
Description
Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase
Time Frame
from baseline (2-week run in) to 6 weeks of treatment
Secondary Outcome Measure Information:
Title
Change in number of Raynaud's Phenomenon attacks
Description
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.
Time Frame
from baseline (2-week run in) to 6 weeks of treatment
Title
Change in duration of Raynaud's Phenomenon attacks
Description
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.
Time Frame
from baseline (2-week run in) to 6 weeks of treatment
Title
Reduction of ulcer burden among secondary Raynaud's Phenomenon patients
Description
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.
Time Frame
from baseline (2-week run in) to 6 weeks of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aaron Waxman, MD/PhD
Organizational Affiliation
Brigham and Womens Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Paul Dellaripa, MD
Organizational Affiliation
Brigham and Womens Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
26914257
Citation
Ennis H, Hughes M, Anderson ME, Wilkinson J, Herrick AL. Calcium channel blockers for primary Raynaud's phenomenon. Cochrane Database Syst Rev. 2016 Feb 25;2(2):CD002069. doi: 10.1002/14651858.CD002069.pub5.
Results Reference
background
PubMed Identifier
22453196
Citation
Roustit M, Hellmann M, Cracowski C, Blaise S, Cracowski JL. Sildenafil increases digital skin blood flow during all phases of local cooling in primary Raynaud's phenomenon. Clin Pharmacol Ther. 2012 May;91(5):813-9. doi: 10.1038/clpt.2011.302. Epub 2012 Mar 28.
Results Reference
background
PubMed Identifier
8923366
Citation
Vayssairat M. Controlled multicenter double blind trial of an oral analog of prostacyclin in the treatment of primary Raynaud's phenomenon. French Microcirculation Society Multicentre Group for the Study of Vascular Acrosyndromes. J Rheumatol. 1996 Nov;23(11):1917-20.
Results Reference
background
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Assess Efficacy of of Oral Treprostinil in Patients With Symptomatic Primary or Secondary Raynaud's Phenomenon
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