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Bosentan in Digital Ulcers (RAPIDS 2 OL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00319696
Recruitment Status : Completed
First Posted : April 27, 2006
Results First Posted : August 8, 2012
Last Update Posted : January 8, 2019
Sponsor:
Information provided by (Responsible Party):
Actelion

Brief Summary:
The aim of the study is to collect long-term efficacy, tolerability and safety data of bosentan in Systemic Sclerosis (SSc) patients suffering from ischemic digital ulcers (DUs).

Condition or disease Intervention/treatment Phase
Digital Ulcers Drug: Bosentan 62.5 mg Drug: Bosentan 125 mg Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 116 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Long-term Bosentan Open Label Extension of the AC-052-331 Study in Systemic Sclerosis Patients With Ischemic Digital Ulcers
Actual Study Start Date : July 8, 2004
Actual Primary Completion Date : January 22, 2009
Actual Study Completion Date : January 22, 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Bosentan

Arm Intervention/treatment
Experimental: Bosentan
Bosentan 62.5 mg tablets b.i.d. for the first 4 weeks followed by bosentan 125 mg b.i.d. thereafter
Drug: Bosentan 62.5 mg
Bosentan 62.5-mg oral tablets twice daily (b.i.d.) for 4 weeks (initial dose)

Drug: Bosentan 125 mg
Bosentan 125-mg oral tablets administered b.i.d. (target dose)




Primary Outcome Measures :
  1. Time to Complete Healing of Each Baseline DU [ Time Frame: Baseline to healing ]
  2. Time to Complete Healing of Each New DU [ Time Frame: New DU occurence to healing ]
  3. Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Dressing [ Time Frame: 80 weeks ]
    SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

  4. Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Arising [ Time Frame: 80 weeks ]
    SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

  5. Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Eating [ Time Frame: 80 weeks ]
    SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

  6. Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Walking [ Time Frame: 80 weeks ]
    SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

  7. Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Hygiene [ Time Frame: 80 weeks ]
    SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

  8. Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Reach [ Time Frame: 80 weeks ]
    SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

  9. Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Grip [ Time Frame: 80 weeks ]
    SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

  10. Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Activity [ Time Frame: 80 weeks ]
    SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.

  11. Mean Changes From Baseline at Each 16 Week Interval up to Week 80 in Overall Hand Pain Related to Finger Ulcers [ Time Frame: 80 weeks ]
    Overall hand pain related to finger ulcers was assessed by the patient using a Visual Analogue Scale. Patients were instructed to score their pain by marking on the continuous 10-cm scale, where 0 (left) was no pain and 100 (right) very severe pain, in response to the question, "How much pain have you had because of your finger ulcers in the past week?" The investigator measured the distance in millimeters between 0 and the patient mark with the ruler provided and recorded the distance.

  12. Mean Change From Baseline at Each 16 Week Interval up to Week 80 in the UK Systemic Sclerosis Functional Score (UKFS) [ Time Frame: 80 weeks ]
    UKFS relates to upper and lower extremity function and muscle weakness. For each item, the patient indicated the responses that best described their current ability: "able to perform in a normal manner," "able to perform with alteration in style," "can only manage with difficulty," and "impossible to achieve." Each response was given an integer from 0 (able to perform in a normal manner) to 3 (impossible to achieve), and the sum of individual responses provided an overall score of 0 to 33. Missing values were replaced with the worst value the patient reported on the other items at that visit.

  13. Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits [ Time Frame: At planned visits up to week 80 ]
    The total number of new DUs per patient observed by the investigator at planned visits and new transient DUs recorded in the patient diary (a patient diary was used to record DUs that might appear and disappear between two planned visits) were assessed at each clinic visit


Secondary Outcome Measures :
  1. Adverse Events up to 24 Hours After Last Study Medication [ Time Frame: 80 weeks ]
    Number of patients with at least one treatment-emergent adverse event. All adverse events that occurred after study drug initiation and up to 24 hours after study drug discontinuation were to be recorded.

  2. Adverse Events Leading to Permanent Discontinuation of the Study Medication [ Time Frame: 80 weeks ]
    Number of patients with an adverse event leading to permanent discontinuation of the study treatment

  3. Serious Adverse Events up to 28 Days After Last Study Medication [ Time Frame: 80 weeks ]
    Number of patients with at least one treatment-emergent serious adverse event (TESAE) were reported. TESAEs are serious AEs that occurred after study drug initiation and up to 28 days after study drug discontinuation. More details on the SAEs are provided in the specific Adverse Events Section



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Patients with SSc according to the classification criteria of the American College of Rheumatology
  2. SSc patients with at least one DU at baseline qualifying as a CU (see definition section 3.2.2)
  3. CU occurred < 3 months and > 1 week prior to randomization. The subset of patients with SSc felt to be at high risk for DUs will be identified in the screening period but will not be eligible for enrollment until a CU has developed
  4. Male or female patients >/= 18 years of age
  5. Women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination
  6. Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile
  7. Signed informed consent.

Exclusion Criteria:

  1. DUs due to condition other than SSc
  2. Severe PAH (WHO class III and IV)
  3. Systolic blood pressure < 85 mmHg
  4. Hemoglobin concentration < 75% of the lower limit of the normal range
  5. AST and/or ALT values greater than 3 times the upper limit of normal
  6. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
  7. Severe malabsorption or any severe organ failure (e.g., lung, kidney) or any life-threatening condition
  8. Pregnancy or breast-feeding
  9. Previous treatment with bosentan
  10. Treatment with any of the following: glibenclamide (glyburide), fluconazole, cyclosporine A, tacrolimus and any other calcineurin inhibitor 1 week prior to randomization
  11. Local injection of botulinum toxin in an affected finger 1 month prior to randomization
  12. Treatment with parenteral prostanoids (prostaglandin E, epoprostenol, treprostinil sodium or other prostacyclin analogs) 3 months prior to randomization
  13. Treatment with inhaled or oral prostanoids one month prior to randomization
  14. Systemic antibiotics to treat infection of DUs 2 weeks prior to randomization
  15. Treatment with phosphodiesterase inhibitors such as sildenafil, except for intermittent treatment of male erectile dysfunction
  16. Body weight < 40 kg
  17. Patient with conditions that prevent compliance with the protocol or adhering to therapy
  18. Patient who received an investigational product within 1 month preceding screening
  19. Known hypersensitivity to bosentan or any of the excipients.

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): NCT00319696


Locations
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Sponsors and Collaborators
Actelion

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Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT00319696    
Other Study ID Numbers: AC-052-333
First Posted: April 27, 2006    Key Record Dates
Results First Posted: August 8, 2012
Last Update Posted: January 8, 2019
Last Verified: December 2018
Keywords provided by Actelion:
digital ulcers
systemic sclerosis
finger ulcers
bosentan
open label
Additional relevant MeSH terms:
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Skin Ulcer
Ulcer
Pathologic Processes
Skin Diseases
Bosentan
Antihypertensive Agents
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action