Alprostadil in Peripheral Arterial Occlusive Disease (PAOD) Stage IV (ESPECIAL)

This study has been completed.
Sponsor:
Collaborator:
Aptiv Solutions
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier:
NCT00596752
First received: December 21, 2007
Last updated: July 21, 2014
Last verified: July 2014

December 21, 2007
July 21, 2014
March 2004
May 2013   (final data collection date for primary outcome measure)
  • Complete Healing of Ischemic Necroses and Ulcerations at 12 Weeks After the End of Study Drug Treatment [ Time Frame: At 12 weeks after the end of study drug treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: At 24 weeks after the end of study drug treatment ] [ Designated as safety issue: No ]
    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.
  • Rate of complete healing of ulcerations after 12 weeks [ Time Frame: 12 weeks ]
  • Frequency of amputations after 24 weeks [ Time Frame: 24 weeks ]
Complete list of historical versions of study NCT00596752 on ClinicalTrials.gov Archive Site
  • Complete Healing of Ischemic Necroses and Ulcerations at 24 Weeks After the End of Study Drug Treatment [ Time Frame: At 24 weeks after the end of study drug treatment ] [ Designated as safety issue: No ]
    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.
  • Intensity of Rest Pain Induced by Ischemic Lesions at 24 Weeks After the End of Study Drug Treatment [ Time Frame: At 24 weeks after the end of study drug treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: At 24 weeks after the end of study drug treatment ] [ Designated as safety issue: No ]
    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 %.
  • Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days) [ Time Frame: During the course of the study (up to 196 days) ] [ Designated as safety issue: No ]
    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 [ Time Frame: At 24 weeks after the end of study drug treatment ] [ Designated as safety issue: No ]
    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.
  • Minor Amputations at 24 Weeks After the End of Study Drug Treatment [ Time Frame: At 24 weeks after the end of study drug treatment ] [ Designated as safety issue: No ]

    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.

  • Revascularization Procedures at 24 Weeks After the End of Study Drug Treatment [ Time Frame: At 24 weeks after the end of study drug treatment ] [ Designated as safety issue: No ]
    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) [ Time Frame: During the course of the study (up to 196 days) ] [ Designated as safety issue: No ]
  • Cardiovascular Mortality During the Course of the Study (up to 196 Days) [ Time Frame: During the course of the study (up to 196 days) ] [ Designated as safety issue: No ]
  • Cardiovascular Morbidity During the Course of the Study (up to 196 Days) [ Time Frame: During the course of the study (up to 196 days) ] [ Designated as safety issue: No ]
    Cardiovascular morbidity is presented as number of subjects with myocardial infarction and/or stroke during the course of the study.
Rate of complete healing of all necroses and ulcerations; Intensity of rest pain; Consumption and type of analgesics; minor amputations [ Time Frame: 24 weeks ]
Not Provided
Not Provided
 
Alprostadil in Peripheral Arterial Occlusive Disease (PAOD) Stage IV
Multinational, Prospective, Randomized, Double-Blind, Placebo-Controlled, Parallel Groups Study to Assess the Efficacy and Safety of Prostaglandin E1 in Subjects With Critical Limb Ischemia (Fontaine Stage IV)

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Peripheral Arterial Occlusive Disease
  • Drug: Alprostadil
    • Active Substance: Prostaglandin E1
    • Pharmaceutical Form: solution for infusion
    • Concentration: 40 μg b.d.
    • Route of Administration: intravenous infusion
    Other Name: Prostavasin
  • Other: Placebo
    • Active Substance: Lactose
    • Pharmaceutical Form: solution for infusion
    • Concentration: 40 μg b.d.
    • Route of Administration: intravenous infusion
  • Experimental: 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.
    Intervention: Drug: Alprostadil
  • Placebo Comparator: 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.
    Intervention: Other: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
840
July 2013
May 2013   (final data collection date for primary outcome measure)

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
Both
45 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Czech Republic,   Germany,   Mexico,   Poland,   Russian Federation,   Ukraine
 
NCT00596752
SP777, 2005-001970-29
Yes
UCB Pharma ( UCB BIOSCIENCES GmbH )
UCB BIOSCIENCES GmbH
Aptiv Solutions
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
UCB Pharma
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP