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

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

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.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Drug: Bosentan; Drug: Antiaggregant therapy; Drug: Statins; Drug: Antihypertensive therapy

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid
    • Getafe, Madrid, Spain, 28901
      • Hospital Universitario de Getafe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the serum levels of Endothelin (ET) respect baseline values	To determine the efficacy of bosentan on the improvement in the endothelin function in patients with Intermittent Claudication due Peripheral Arterial Disease	1 Year
Change in the serum levels of C-reactive protein (CRP) respect baseline values	To determine the efficacy of bosentan on the improvement in inflammatory status in patients with Intermittent Claudication due Peripheral Arterial Disease. CRP for the treatment group and control group, at each visit after baseline : 1 month, 3 months, 6 months and 12 months	1 Year

Collaborators and Investigators

• Sponsor: Hospital Universitario Getafe
• Investigators: Principal Investigator: De Haro Joaquin, MD, PhD, Hospital Universitario de Getafe

Publications and helpful links

General Publications

• De Haro J, Bleda S, Varela C, Esparza L, Acin F; Bosentan Population-Based Randomized Trial for Clinical and Endothelial Function Assessment on Endothelin Antagonist Therapy in Patients With Intermittent Claudication CLAU Investigators. Effect of Bosentan on Claudication Distance and Endothelium-Dependent Vasodilation in Hispanic Patients With Peripheral Arterial Disease. Am J Cardiol. 2016 Jan 15;117(2):295-301. doi: 10.1016/j.amjcard.2015.10.032. Epub 2015 Nov 6.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: October 30, 2012
• First Submitted That Met QC Criteria: November 28, 2012
• First Posted (Estimate): November 30, 2012

Study Record Updates

• Last Update Posted (Estimate): November 30, 2012
• Last Update Submitted That Met QC Criteria: November 28, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Bosentan; Peripheral Arterial Disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases; Intermittent Claudication; Molecular Mechanisms of Pharmacological Action; Endothelin Receptor Antagonists; Antihypertensive Agents; Bosentan
• Other Study ID Numbers: NTC25102012; E.C.13/2009.CEIC10 (Other Grant/Funding Number: E.C.13/2009.CEIC10)