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

Primary Purpose

Peripheral Arterial Occlusive Disease

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Alprostadil
Placebo
Sponsored by
UCB BIOSCIENCES GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral Arterial Occlusive Disease focused on measuring Alprostadil, Prostavasin, PAOD, Fontaine Stage IV

Eligibility Criteria

45 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • 404
  • 414
  • 1
  • 502
  • 505
  • 501
  • 306
  • 321
  • 320
  • 314
  • 315
  • 316
  • 317
  • 301
  • 304
  • 319
  • 307
  • 308
  • 309
  • 318
  • 312
  • 322
  • 246
  • 205
  • 244
  • 223
  • 247
  • 228
  • 242
  • 227
  • 201
  • 202
  • 203
  • 209
  • 219
  • 220
  • 230
  • 248
  • 231
  • 232
  • 222
  • 217
  • 206
  • 225
  • 236
  • 239
  • 224
  • 218
  • 237
  • 210
  • 212
  • 213
  • 214
  • 215
  • 216
  • 243
  • 238
  • 234
  • 241
  • 240
  • 221
  • 112
  • 109
  • 110
  • 114
  • 111
  • 101
  • 102
  • 103
  • 104
  • 105
  • 106
  • 118
  • 119
  • 113
  • 116
  • 107
  • 108

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Alprostadil

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Complete Healing of Ischemic Necroses and Ulcerations 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
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
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
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
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)
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
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
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
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)
Cardiovascular Mortality During the Course of the Study (up to 196 Days)
Cardiovascular Morbidity 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.

Full Information

First Posted
December 21, 2007
Last Updated
March 8, 2018
Sponsor
UCB BIOSCIENCES GmbH
Collaborators
Aptiv Solutions
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1. Study Identification

Unique Protocol Identification Number
NCT00596752
Brief Title
Alprostadil in Peripheral Arterial Occlusive Disease (PAOD) Stage IV
Acronym
ESPECIAL
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
March 2004 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UCB BIOSCIENCES GmbH
Collaborators
Aptiv Solutions

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Arterial Occlusive Disease
Keywords
Alprostadil, Prostavasin, PAOD, Fontaine Stage IV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
840 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alprostadil
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Alprostadil
Other Intervention Name(s)
Prostavasin
Intervention Description
Active Substance: Prostaglandin E1 Pharmaceutical Form: solution for infusion Concentration: 40 μg b.d. Route of Administration: intravenous infusion
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Active Substance: Lactose Pharmaceutical Form: solution for infusion Concentration: 40 μg b.d. Route of Administration: intravenous infusion
Primary Outcome Measure Information:
Title
Complete Healing of Ischemic Necroses and Ulcerations at 12 Weeks After the End of Study Drug Treatment
Description
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.
Time Frame
At 12 weeks after the end of study drug treatment
Title
Occurrence of Major Amputations at 24 Weeks After the End of Study Drug Treatment
Description
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.
Time Frame
At 24 weeks after the end of study drug treatment
Secondary Outcome Measure Information:
Title
Complete Healing of Ischemic Necroses and Ulcerations at 24 Weeks After the End of Study Drug Treatment
Description
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.
Time Frame
At 24 weeks after the end of study drug treatment
Title
Intensity of Rest Pain Induced by Ischemic Lesions at 24 Weeks After the End of Study Drug Treatment
Description
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.
Time Frame
At 24 weeks after the end of study drug treatment
Title
Increase/Decrease in Ulcer Area of ≥ 50 % at 24 Weeks After the End of Study Drug Treatment
Description
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 %.
Time Frame
At 24 weeks after the end of study drug treatment
Title
Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days)
Description
The number of subjects who used analgesics are summarized for different time points/intervals during the course of the study.
Time Frame
During the course of the study (up to 196 days)
Title
Systolic Pressure at Ankle Level at 24 Weeks After the End of Study Drug Treatment
Description
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.
Time Frame
At 24 weeks after the end of study drug treatment
Title
Minor Amputations at 24 Weeks After the End of Study Drug Treatment
Description
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.
Time Frame
At 24 weeks after the end of study drug treatment
Title
Revascularization Procedures at 24 Weeks After the End of Study Drug Treatment
Description
The number of subjects with revascularization prior to or at 24 weeks after the end of study drug treatment is presented below.
Time Frame
At 24 weeks after the end of study drug treatment
Title
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)
Title
Cardiovascular Mortality During the Course of the Study (up to 196 Days)
Time Frame
During the course of the study (up to 196 days)
Title
Cardiovascular Morbidity During the Course of the Study (up to 196 Days)
Description
Cardiovascular morbidity is presented as number of subjects with myocardial infarction and/or stroke during the course of the study.
Time Frame
During the course of the study (up to 196 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
UCB Clinical Trial Call Center
Organizational Affiliation
+1 877 822 9493 (UCB)
Official's Role
Study Director
Facility Information:
Facility Name
404
City
Plzen
Country
Czechia
Facility Name
414
City
Usti Nad Labem
Country
Czechia
Facility Name
1
City
Karlsbad
Country
Germany
Facility Name
502
City
Aguascalientes
Country
Mexico
Facility Name
505
City
Merida
Country
Mexico
Facility Name
501
City
Queretaro
Country
Mexico
Facility Name
306
City
Bydgoszcz
Country
Poland
Facility Name
321
City
Konskie
Country
Poland
Facility Name
320
City
Krakow
Country
Poland
Facility Name
314
City
Lublin
Country
Poland
Facility Name
315
City
Lublin
Country
Poland
Facility Name
316
City
Poznan
Country
Poland
Facility Name
317
City
Poznan
Country
Poland
Facility Name
301
City
Szczecin
Country
Poland
Facility Name
304
City
Szczecin
Country
Poland
Facility Name
319
City
Warsaw
Country
Poland
Facility Name
307
City
Warszawa
Country
Poland
Facility Name
308
City
Warszawa
Country
Poland
Facility Name
309
City
Warszawa
Country
Poland
Facility Name
318
City
Warszawa
Country
Poland
Facility Name
312
City
Wroclaw
Country
Poland
Facility Name
322
City
Zamosc
Country
Poland
Facility Name
246
City
Barnaul
Country
Russian Federation
Facility Name
205
City
Chelyabinsk
Country
Russian Federation
Facility Name
244
City
Chelyabinsk
Country
Russian Federation
Facility Name
223
City
Ekaterinburg
Country
Russian Federation
Facility Name
247
City
Ekaterinburg
Country
Russian Federation
Facility Name
228
City
Irkutsk
Country
Russian Federation
Facility Name
242
City
Kazan
Country
Russian Federation
Facility Name
227
City
Kemerovo
Country
Russian Federation
Facility Name
201
City
Moscow
Country
Russian Federation
Facility Name
202
City
Moscow
Country
Russian Federation
Facility Name
203
City
Moscow
Country
Russian Federation
Facility Name
209
City
Moscow
Country
Russian Federation
Facility Name
219
City
Moscow
Country
Russian Federation
Facility Name
220
City
Moscow
Country
Russian Federation
Facility Name
230
City
Moscow
Country
Russian Federation
Facility Name
248
City
Moscow
Country
Russian Federation
Facility Name
231
City
Novosibirsk
Country
Russian Federation
Facility Name
232
City
Novosibirsk
Country
Russian Federation
Facility Name
222
City
Omsk
Country
Russian Federation
Facility Name
217
City
Petrozavodsk
Country
Russian Federation
Facility Name
206
City
Rostov-on-Don
Country
Russian Federation
Facility Name
225
City
Rostov-on-Don
Country
Russian Federation
Facility Name
236
City
Rostov-on-Don
Country
Russian Federation
Facility Name
239
City
Rostov-on-Don
Country
Russian Federation
Facility Name
224
City
Ryazan
Country
Russian Federation
Facility Name
218
City
Samara
Country
Russian Federation
Facility Name
237
City
Saratov
Country
Russian Federation
Facility Name
210
City
St Petersburg
Country
Russian Federation
Facility Name
212
City
St Petersburg
Country
Russian Federation
Facility Name
213
City
St Petersburg
Country
Russian Federation
Facility Name
214
City
St Petersburg
Country
Russian Federation
Facility Name
215
City
St Petersburg
Country
Russian Federation
Facility Name
216
City
St Petersburg
Country
Russian Federation
Facility Name
243
City
Tula
Country
Russian Federation
Facility Name
238
City
Tumen
Country
Russian Federation
Facility Name
234
City
Tver
Country
Russian Federation
Facility Name
241
City
Ufa
Country
Russian Federation
Facility Name
240
City
Volgograd
Country
Russian Federation
Facility Name
221
City
Yaroslavl
Country
Russian Federation
Facility Name
112
City
Dnipropetrovsk
Country
Ukraine
Facility Name
109
City
Donetsk
Country
Ukraine
Facility Name
110
City
Donetsk
Country
Ukraine
Facility Name
114
City
Ivano-Frankivsk
Country
Ukraine
Facility Name
111
City
Kharkov
Country
Ukraine
Facility Name
101
City
Kiev
Country
Ukraine
Facility Name
102
City
Kiev
Country
Ukraine
Facility Name
103
City
Kiev
Country
Ukraine
Facility Name
104
City
Kiev
Country
Ukraine
Facility Name
105
City
Kiev
Country
Ukraine
Facility Name
106
City
Lviv
Country
Ukraine
Facility Name
118
City
Odessa
Country
Ukraine
Facility Name
119
City
Odessa
Country
Ukraine
Facility Name
113
City
Uzhgorod
Country
Ukraine
Facility Name
116
City
Vinnytsya
Country
Ukraine
Facility Name
107
City
Zaporozhye
Country
Ukraine
Facility Name
108
City
Zaporozhye
Country
Ukraine

12. IPD Sharing Statement

Citations:
PubMed Identifier
28189475
Citation
Lawall H, Pokrovsky A, Checinski P, Ratushnyuk A, Hamm G, Randerath O, Grieger F, Bentz JWG. Efficacy and Safety of Alprostadil in Patients with Peripheral Arterial Occlusive Disease Fontaine Stage IV: Results of a Placebo Controlled Randomised Multicentre Trial (ESPECIAL). Eur J Vasc Endovasc Surg. 2017 Apr;53(4):559-566. doi: 10.1016/j.ejvs.2016.12.035. Epub 2017 Feb 8.
Results Reference
result
Links:
URL
http://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls

Learn more about this trial

Alprostadil in Peripheral Arterial Occlusive Disease (PAOD) Stage IV

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