Safety and Efficacy Study of Bosentan for Intermittent Claudication in Peripheral Arterial Disease

Study Overview
=================
Brief Summary
-----------------
A prospective study, proof-of concept, randomized, controlled, parallel groups, simple blind was performed in 30 male patients (50-60 years old) with Intermittent Claudication (Rutherford category 1-2) recently diagnosed and clinical manifestations not exceeding 6 months with hypertension and/or dyslipidemia as unique co-morbility disorders. After a period of stabilization of the claudication distance in the Stress test (12.5%, 3.2 km/h) during 2 weeks, were randomized 1:1 to the experimental arm (Bosentan 62.5 mg twice daily/four weeks and 125 mg twice daily/eight weeks) or control group.

Official Title
-----------------
CLAU Test Results (CLinical Assessment And Endothelin fUnction Assessment After Endothelin Receptor Antagonist) : Randomized Controlled Clinical Trial of Bosentan for Intermittent Claudication in Peripheral Arterial Disease

Conditions
-----------------
Peripheral Arterial Disease

Intervention / Treatment
-----------------
* Drug: Bosentan
* Drug: Antiaggregant therapy
* Drug: Statins
* Drug: Antihypertensive therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Arterial hypertension and hypercholesterolemia ABI <0,9 Positive claudiometry with a claudication distance between 50 and 500 Exclusion Criteria: surgical patient Previous revascularization procedure in the Member studied Smoker Uncontrolled hypertension Cardiac Stress Test unfinished Prior DVT Concomitant severe disease Obesity

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antiaggregants & Statins & Antihypertensives & Bosentan<br>Bosentan 62.5 mg/12 hours (first four weeks) and 125 mg/12 hours (eight weeks) plus Antiaggregant therapy (AAS 100mg/d or Clopidogrel 75mg/d), Statins and Antihypertensive therapy | Drug: Bosentan<br>* Bosentan 62.5 mg/12 hours (first four weeks) and 125 mg/12 hours (eight weeks)<br>* Other names: Tracleer;Drug: Antiaggregant therapy<br>* AAS 100mg/d or Clopidogrel 75mg/d<br>Drug: Statins<br> <br> Drug: Antihypertensive therapy<br> <br> |
| Active Comparator: Antiaggregants & Statins & Antihypertensives<br>Antiaggregant therapy (AAS 100 mg/d or Clopidogrel 75 mg/d), Statins, Antihypertensive therapy | Drug: Antiaggregant therapy<br>* AAS 100mg/d or Clopidogrel 75mg/d<br>Drug: Statins<br> <br> Drug: Antihypertensive therapy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Absolute Claudication Distance (ACD) respect baseline values | To determine the efficacy of bosentan on the improvement in the absolute claudication distance in the exercise in patients with Intermittent Claudication due Peripheral Arterial Disease. ACD and percentage of change, both for the treatment group and control group, at each visit after baseline : 1 month, 3 months, 6 months and 12 months | 1 Year | 
| Change in flow-mediated arterial dilation (FMAD) respect baseline values | To determine the efficacy of bosentan on the improvement in the overall endothelin function in patients with Intermittent Claudication due Peripheral Arterial Disease FMAD for the treatment group and control group, at each visit after baseline : 1 month, 3 months, 6 months and 12 months | 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Analytical plasma values at each visit respect baseline values | Safety of Bosentan in patients with Intermittent Claudication due Peripheral Arterial Disease. Analytical values : plasma electrolyte values, hepatic function, renal function, coagulation profiles, peripheral blood cell count | 1 Year | 
| Change in the ankle brachial index (ABI) respect baseline values | Efficacy of bosentan on the improvement in the hemodynamic states in patients with Intermittent Claudication due Peripheral Arterial Disease. ABI for the treatment group and control group, at each visit after baseline : 1 month, 3 months, 6 months and 12 months | 1 Year | 
| Change in subjective claudication distance (SCD) reported by the patient, as is defined in the Walking Impairment Questionnaire (WIQ), respect baseline values | Efficacy of bosentan on the improvement of functional status (symptoms of claudication) in patients with Intermittent Claudication due Peripheral Arterial Disease SCD for the treatment group and control group, at each visit after baseline : 1 month, 3 months, 6 months and 12 months | 1 Year | 
| Occurrence of Adverse events during the study | Safety of Bosentan in patients with Intermittent Claudication due Peripheral Arterial Disease. | 1 Year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bosentan, Peripheral Arterial Disease