Alprostadil in Peripheral Arterial Occlusive Disease (PAOD) Stage IV

Phase 4

Completed

Conditions: Peripheral Arterial Occlusive Disease

Interventions: Other: Placebo
Drug: Alprostadil

Registration Number: NCT00596752

Lead Sponsor: UCB BIOSCIENCES GmbH

Brief Summary: The study is to confirmatorily show a superior effect of Alprostadil compared to placebo on the rate of complete healing of ischemic necroses and ulcerations as well as on the frequency and height of major amputations in patients suffering from PAOD stage IV.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 840

Inclusion Criteria

Subject is at least 45 years of age
Subjects with macro-angiopathy, proven PAOD Stage IV with up to 2 ischaemic skin lesions for more than 2 weeks
Subject has a complete angiography of pelvis, thigh and calf within one month of inclusion
Systolic ankle pressure ≤ 70 mmHg in subjects without media sclerosis of the lower limb artery or systolic big toe pressure ≤ 50 mmHg in diabetics with media sclerosis of the lower limb artery
Subject is not in the position to be primarily revascularized or refuses surgery

Exclusion Criteria

Imminent or foreseeable amputation
Major amputation on the affected extremity
History of chronic alcohol or drug abuse
More than two ischemic ulcerations
One ulcer ≥ 6 cm^2, both ulcers ≤ 1 cm^2 or at least one ulcer affecting the bone or tendons
Acute ischemia and peripheral vascular disorders of inflammatory or immunologic origin
Neuropathic or venous ulcers
Buerger's disease
Septic gangrene
Use of vasoactive medication or prostaglandins
Treatment with prostanoids within 3 months prior to inclusion
Surgical or interventional measures performed on the affected extremity within 3 months prior to study drug treatment

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks.
Alprostadil	Alprostadil	Prostavasin® 40 μg will be infused intravenously twice daily over 2 hours in 50 to 150 ml isotonic sodium chloride solution during a Treatment Phase of 4 weeks.

Primary Outcome Measures

Name	Time	Method
Complete Healing of Ischemic Necroses and Ulcerations at 12 Weeks After the End of Study Drug Treatment	At 12 weeks after the end of study drug treatment	The assessment of ulcer area was collected per lesion with up to 2 lesions per subject (both legs could be affected). In the analysis a subject is only considered completely healed at a time point, if all ischemic lesions are reported as completely healed at that time point.
Occurrence of Major Amputations at 24 Weeks After the End of Study Drug Treatment	At 24 weeks after the end of study drug treatment	Assessment of amputations was collected per leg affected by a lesion with up to 2 lesions per subject. Amputations were regarded as major if they were performed at the ankle joint level or above. Amputations of toes or part of the foot leaving a stump thereon the subject can walk were regarded as minor. An affected leg is defined as a leg with at least 1 lesion on Study Day -6 to -2 and only amputations of affected legs are considered in the efficacy analysis of amputations. A subject is counted as major/minor amputated, if at least 1 affected leg was major/minor amputated.

Secondary Outcome Measures

Name	Time	Method
Complete Healing of Ischemic Necroses and Ulcerations at 24 Weeks After the End of Study Drug Treatment	At 24 weeks after the end of study drug treatment	The assessment of ulcer area was collected per lesion with up to 2 lesions per subject (both legs could be affected). In the analysis a subject is only considered completely healed at a time point, if all ischemic lesions are reported as completely healed at that time point.
Revascularization Procedures at 24 Weeks After the End of Study Drug Treatment	At 24 weeks after the end of study drug treatment	The number of subjects with revascularization prior to or at 24 weeks after the end of study drug treatment is presented below.
All-cause Mortality During the Course of the Study (up to 196 Days)	During the course of the study (up to 196 days)
Minor Amputations at 24 Weeks After the End of Study Drug Treatment	At 24 weeks after the end of study drug treatment	Assessment of amputations was collected per leg affected by a lesion with up to 2 lesions per subject. Amputations were regarded as major if they were performed at the ankle joint level or above. Amputations of toes or part of the foot leaving a stump thereon the subject can walk were regarded as minor. An affected leg is defined as a leg with at least 1 lesion on Study Day -6 to -2 and only amputations of affected legs are considered in the efficacy analysis of amputations. A subject is counted as major/minor amputated, if at least 1 affected leg was major/minor amputated. The number of subjects with minor amputation prior to or at 24 weeks after the end of study drug treatment is presented below.
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days)	During the course of the study (up to 196 days)	The number of subjects who used analgesics are summarized for different time points/intervals during the course of the study.
Systolic Pressure at Ankle Level at 24 Weeks After the End of Study Drug Treatment	At 24 weeks after the end of study drug treatment	Systolic pressure at ankle level was measured at the Arteria tibialis posterior and the Arteria dorsalis pedis. Two individual series of measurements of arterial pressures per subject across the assessed visits were selected for the analysis. For the first analysis (worst change analysis) the series of measurements in the one artery which has the worst change from Baseline at the final measurement was used. For the second analysis (worst value analysis) the series of measurements which has the worst final post-Baseline measurement was used. The series relevant for the analyses was selected from the series for the affected leg or legs only. The selection is 1 out of up to 4 series available per subject. Series without Baseline value and series with at least 1 measurement of more than 150 mmHg were excluded from the selection process due to the suspicion of media sclerosis of the lower limb artery.
Intensity of Rest Pain Induced by Ischemic Lesions at 24 Weeks After the End of Study Drug Treatment	At 24 weeks after the end of study drug treatment	Visit values of intensity of rest pain from a visual analogue scale, ranging from 0 mm (no pain) to 100 mm (maximum conceivable pain), had to be reported in the case of presence of rest pain only. If the leading question in regard to the presence of rest pain is answered with "No" and no visit value is specified, the visit value will be set to 0 for the analysis.
Increase/Decrease in Ulcer Area of ≥ 50 % at 24 Weeks After the End of Study Drug Treatment	At 24 weeks after the end of study drug treatment	In case of two ulcers the worse ulcer status is analyzed. The categories of investigator assessment are: complete healing, decrease by ≥ 50 %, unchanged, increase by ≥ 50 %.
Cardiovascular Mortality During the Course of the Study (up to 196 Days)	During the course of the study (up to 196 days)
Cardiovascular Morbidity During the Course of the Study (up to 196 Days)	During the course of the study (up to 196 days)	Cardiovascular morbidity is presented as number of subjects with myocardial infarction and/or stroke during the course of the study.

Trial Locations

Locations (78): 404
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Plzen, Czechia
414
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Usti Nad Labem, Czechia
1
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Karlsbad, Germany
502
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Aguascalientes, Mexico
505
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Merida, Mexico
501
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Queretaro, Mexico
306
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Bydgoszcz, Poland
321
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Konskie, Poland
320
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Krakow, Poland
314
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Lublin, Poland
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404
🇨🇿Plzen, Czechia