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, Inc. ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier:
NCT00596752
First received: December 21, 2007
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Peripheral Arterial Occlusive Disease
Drug: Alprostadil
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by UCB, Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 840
Study Start Date: March 2004
Study Completion Date: July 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Alprostadil
  • Active Substance: Prostaglandin E1
  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Other Name: Prostavasin
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.
Other: Placebo
  • Active Substance: Lactose
  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00596752

  Hide Study Locations
Locations
Czech Republic
404
Plzen, Czech Republic
414
Usti Nad Labem, Czech Republic
Germany
1
Karlsbad, Germany
Mexico
502
Aguascalientes, Mexico
505
Merida, Mexico
501
Queretaro, Mexico
Poland
306
Bydgoszcz, Poland
321
Konskie, Poland
320
Krakow, Poland
314
Lublin, Poland
315
Lublin, Poland
316
Poznan, Poland
317
Poznan, Poland
301
Szczecin, Poland
304
Szczecin, Poland
319
Warsaw, Poland
307
Warszawa, Poland
308
Warszawa, Poland
309
Warszawa, Poland
318
Warszawa, Poland
312
Wroclaw, Poland
322
Zamosc, Poland
Russian Federation
246
Barnaul, Russian Federation
205
Chelyabinsk, Russian Federation
244
Chelyabinsk, Russian Federation
223
Ekaterinburg, Russian Federation
247
Ekaterinburg, Russian Federation
228
Irkutsk, Russian Federation
242
Kazan, Russian Federation
227
Kemerovo, Russian Federation
201
Moscow, Russian Federation
202
Moscow, Russian Federation
203
Moscow, Russian Federation
219
Moscow, Russian Federation
220
Moscow, Russian Federation
230
Moscow, Russian Federation
209
Moscow, Russian Federation
248
Moscow, Russian Federation
231
Novosibirsk, Russian Federation
232
Novosibirsk, Russian Federation
222
Omsk, Russian Federation
217
Petrozavodsk, Russian Federation
206
Rostov-on-Don, Russian Federation
225
Rostov-on-Don, Russian Federation
236
Rostov-on-Don, Russian Federation
239
Rostov-on-Don, Russian Federation
224
Ryazan, Russian Federation
218
Samara, Russian Federation
237
Saratov, Russian Federation
213
St Petersburg, Russian Federation
210
St Petersburg, Russian Federation
212
St Petersburg, Russian Federation
214
St Petersburg, Russian Federation
215
St Petersburg, Russian Federation
216
St Petersburg, Russian Federation
243
Tula, Russian Federation
238
Tumen, Russian Federation
234
Tver, Russian Federation
241
Ufa, Russian Federation
240
Volgograd, Russian Federation
221
Yaroslavl, Russian Federation
Ukraine
112
Dnipropetrovsk, Ukraine
109
Donetsk, Ukraine
110
Donetsk, Ukraine
114
Ivano-Frankivsk, Ukraine
111
Kharkov, Ukraine
101
Kiev, Ukraine
102
Kiev, Ukraine
103
Kiev, Ukraine
104
Kiev, Ukraine
105
Kiev, Ukraine
106
Lviv, Ukraine
118
Odessa, Ukraine
119
Odessa, Ukraine
113
Uzhgorod, Ukraine
116
Vinnytsya, Ukraine
107
Zaporozhye, Ukraine
108
Zaporozhye, Ukraine
Sponsors and Collaborators
UCB BIOSCIENCES GmbH
Aptiv Solutions
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

Additional Information:
No publications provided

Responsible Party: UCB, Inc. ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier: NCT00596752     History of Changes
Other Study ID Numbers: SP777, 2005-001970-29
Study First Received: December 21, 2007
Results First Received: May 5, 2014
Last Updated: July 21, 2014
Health Authority: Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Mexico: Federal Commission for Protection Against Health Risks
Poland: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Ukraine: State Pharmacological Center - Ministry of Health

Keywords provided by UCB, Inc.:
Alprostadil
Prostavasin
PAOD
Fontaine Stage IV

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Peripheral Arterial Disease
Vascular Diseases
Cardiovascular Diseases
Atherosclerosis
Arteriosclerosis
Peripheral Vascular Diseases
Alprostadil
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Urological Agents

ClinicalTrials.gov processed this record on August 20, 2014