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Trial record 1 of 1 for:    NCT00596752
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Alprostadil in Peripheral Arterial Occlusive Disease (PAOD) Stage IV (ESPECIAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00596752
Recruitment Status : Completed
First Posted : January 17, 2008
Results First Posted : August 12, 2014
Last Update Posted : April 4, 2018
Sponsor:
Collaborator:
Aptiv Solutions
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES GmbH )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Peripheral Arterial Occlusive Disease
Interventions Drug: Alprostadil
Other: Placebo
Enrollment 840
Recruitment Details This study started to enroll subjects in March 2004 in order to end up with 840 enrolled subjects. The study was conducted using a two-stage group sequential adaptive design with possible sample size adjustment after the planned interim analysis, which was performed after stage 1. After the interim analysis subjects were included in stage 2.
Pre-assignment Details Participant Flow refers to the Randomized Set (RS). RS consists of all subjects randomized into the study who have completed the study or terminated prematurely.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Period Title: Overall Study
Started 415 425
Randomized and Treated 415 424
Completed 289 282
Not Completed 126 143
Reason Not Completed
Other Reason             44             49
Adverse Event             34             34
Lost to Follow-up             22             38
Withdrawal by Subject             12             9
Unsatisfactory Compliance             9             6
Lack of Efficacy             4             7
Protocol Violation             1             0
Arm/Group Title Alprostadil Placebo Total
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Total of all reporting groups
Overall Number of Baseline Participants 416 423 839
Hide Baseline Analysis Population Description
Baseline Characteristics refer to the Safety Set including all randomized subjects who received at least one dose of trial medication. Subjects were analyzed according to the actual treatment received. 4 PBO subjects were treated with Alprostadil, 3 Alprostadil subjects were treated with PBO.1 PBO subject withdrew prior to start of study treatment.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 416 participants 423 participants 839 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
153
  36.8%
170
  40.2%
323
  38.5%
>=65 years
263
  63.2%
253
  59.8%
516
  61.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 416 participants 423 participants 839 participants
66.8  (8.5) 66.4  (9.3) 66.6  (8.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 416 participants 423 participants 839 participants
Female
123
  29.6%
117
  27.7%
240
  28.6%
Male
293
  70.4%
306
  72.3%
599
  71.4%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 416 participants 423 participants 839 participants
75.4  (11.9) 76.6  (12.6) 76.0  (12.2)
1.Primary Outcome
Title Complete Healing of Ischemic Necroses and Ulcerations at 12 Weeks After the End of Study Drug Treatment
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF) in case of missing values. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Overall Number of Participants Analyzed 414 424
Measure Type: Number
Unit of Measure: participants
Stage 1 (n=253, n=251) 49 43
Stage 2 (n=161, n=173) 27 30
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alprostadil, Placebo
Comments

Primary goal was to test the following null hypothesis:

H01: πhealingPGE1≤ πhealingPlacebo, with πhealing=proportion of subjects with complete ulcer healing. The planned information rate for stage 1 of the two-stage group sequential test design with an overall one-sided comparison-wise α=0.0125 for this co-primary endpoint is given by 0.83.

This is the statistical analysis of stage 1.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2587
Comments For confirmatory hypothesis testing the p-values of the normal approximation test for comparing two rates was used as input for the weighted inverse normal method. The 1-sided boundary p-value for stage 1 is given by p1=0.00587.
Method Cochran-Mantel-Haenszel
Comments The 2 primary endpoints were tested at one-sided 0.0125 each so that the overall type I error rate of 0.025 was controlled in a strong sense.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alprostadil, Placebo
Comments

Primary goal was to test the following null hypothesis:

H01: πhealingPGE1≤ πhealingPlacebo, with πhealing=proportion of subjects with complete ulcer healing.

This is the statistical analysis of stage 1 and stage 2 combined.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3463
Comments For confirmatory hypothesis testing the p-values of the normal approximation test for comparing two rates was used as input for the weighted inverse normal method. The 1-sided boundary p-value for stage 1 and 2 combined is given by p2=0.01085.
Method Cochran-Mantel-Haenszel
Comments The 2 primary endpoints were tested at one-sided 0.0125 each so that the overall type I error rate of 0.025 was controlled in a strong sense.
2.Primary Outcome
Title Occurrence of Major Amputations at 24 Weeks After the End of Study Drug Treatment
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF) in case of missing values. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Overall Number of Participants Analyzed 414 424
Measure Type: Number
Unit of Measure: participants
Stage 1 (n=253, n=251) 32 49
Stage 2 (n=161, n=173) 20 13
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alprostadil, Placebo
Comments

Primary goal was to test the following null hypothesis:

H02: πampPGE1≥ πampPlacebo, with πamp=proportion of subjects with major amputations.

The planned information rate for stage 1 of the two-stage group sequential test design with an overall one-sided comparison-wise α=0.0125 for this co-primary endpoint is given by 0.83.

This is the statistical analysis of stage 1.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0173
Comments For confirmatory hypothesis testing the p-values of the normal approximation test for comparing two rates was used as input for the weighted inverse normal method. The 1-sided boundary p-value for stage 1 is given by p1=0.00587.
Method Cochran-Mantel-Haenszel
Comments The 2 primary endpoints were tested at one-sided 0.0125 each so that the overall type I error rate of 0.025 was controlled in a strong sense.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alprostadil, Placebo
Comments

Primary goal was to test the following null hypothesis:

H02: πampPGE1≥ πampPlacebo, with πamp=proportion of subjects with major amputations.

This is the statistical analysis of stage 1 and stage 2 combined.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1154
Comments For confirmatory hypothesis testing the p-values of the normal approximation test for comparing two rates was used as input for the weighted inverse normal method. The 1-sided boundary p-value for stage 1 and 2 combined is given by p2=0.01085.
Method Cochran-Mantel-Haenszel
Comments The 2 primary endpoints were tested at one-sided 0.0125 each so that the overall type I error rate of 0.025 was controlled in a strong sense.
3.Secondary Outcome
Title Complete Healing of Ischemic Necroses and Ulcerations at 24 Weeks After the End of Study Drug Treatment
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 838 subjects in the Full Analysis Set (FAS), 568 are included in the analysis of this outcome measure. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Overall Number of Participants Analyzed 289 279
Measure Type: Number
Unit of Measure: participants
108 103
4.Secondary Outcome
Title Intensity of Rest Pain Induced by Ischemic Lesions at 24 Weeks After the End of Study Drug Treatment
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF) in case of missing values. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Overall Number of Participants Analyzed 414 424
Mean (Standard Deviation)
Unit of Measure: millimeters (mm)
17.57  (25.33) 16.38  (25.08)
5.Secondary Outcome
Title Increase/Decrease in Ulcer Area of ≥ 50 % at 24 Weeks After the End of Study Drug Treatment
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 838 subjects in the Full Analysis Set (FAS), 465 are included in the analysis of this outcome measure. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Overall Number of Participants Analyzed 233 232
Measure Type: Number
Unit of Measure: participants
Complete healing 101 98
Decrease by >= 50 % 57 56
Remains unchanged 45 48
Increase by >= 50 % 30 30
6.Secondary Outcome
Title Consumption and Type of Analgesic Medication During the Course of the Study (up to 196 Days)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Overall Number of Participants Analyzed 414 424
Measure Type: Number
Unit of Measure: participants
Prior to treatment (n=414, n=424) 300 318
Concomitant, Study Day 1 (n=414, n=424) 292 314
Concomitant, Study Day 2 (n=414, n=424) 295 313
Concomitant, Study Day 3 (n=413, n=424) 295 317
Concomitant, Study Day 4 (n=412, n=423) 292 316
Concomitant, Study Day 5 (n=411, n=423) 294 311
Concomitant, Study Day 6 (n=411, n=423) 290 312
Concomitant, Study Day 7 (n=409, n=422) 290 306
Concomitant, Week 2 (n=409, n=422) 292 308
Concomitant, Week 3 (n=399, n=416) 259 284
Concomitant, Week 4 (n=393, n=404) 238 257
Post treatment, Study Days 29-42 (n=348, n=354) 170 191
Post treatment, Study Days 43-56 (n=361, n=370) 164 173
Post treatment, Study Days 57-70 (n=361, n=346) 155 155
Post treatment, Study Days 71-84 (n=352, n=344) 146 148
Post treatment, Study Days 85-98 (n=341, n=339) 143 140
Post treatment, Study Days 99-112 (n=321, n=318) 132 127
Post treatment, Study Days 113-140 (n=309, n=301) 122 117
Post treatment, Study Days 141-168 (n=306, n=304) 118 109
Post treatment, Study Days 169-196 (n=272, n=271) 98 90
7.Secondary Outcome
Title Systolic Pressure at Ankle Level at 24 Weeks After the End of Study Drug Treatment
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) with Last Observation Carried Forward (LOCF) in case of missing values. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Overall Number of Participants Analyzed 383 394
Mean (Standard Deviation)
Unit of Measure: mmHg
Worst change analysis 42.83  (30.16) 39.47  (28.32)
Worst value analysis 39.39  (29.92) 36.45  (27.19)
8.Secondary Outcome
Title Minor Amputations at 24 Weeks After the End of Study Drug Treatment
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 838 subjects in the Full Analysis Set (FAS), 613 are included in the analysis of this outcome measure. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Overall Number of Participants Analyzed 316 297
Measure Type: Number
Unit of Measure: participants
65 40
9.Secondary Outcome
Title Revascularization Procedures at 24 Weeks After the End of Study Drug Treatment
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 838 subjects in the Full Analysis Set (FAS), 577 are included in the analysis of this outcome measure. FAS consists of all randomized subjects who received at least one dose of trial medication and who provide valid data to assess at least one of the primary efficacy endpoints.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Overall Number of Participants Analyzed 294 283
Measure Type: Number
Unit of Measure: participants
6 7
10.Secondary Outcome
Title All-cause Mortality During the Course of the Study (up to 196 Days)
Hide Description [Not Specified]
Time Frame During the course of the study (up to 196 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set consists of all randomized subjects who received at least one dose of trial medication.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Overall Number of Participants Analyzed 416 423
Measure Type: Number
Unit of Measure: participants
20 15
11.Secondary Outcome
Title Cardiovascular Mortality During the Course of the Study (up to 196 Days)
Hide Description [Not Specified]
Time Frame During the course of the study (up to 196 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set consists of all randomized subjects who received at least one dose of trial medication.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Overall Number of Participants Analyzed 416 423
Measure Type: Number
Unit of Measure: participants
11 14
12.Secondary Outcome
Title Cardiovascular Morbidity During the Course of the Study (up to 196 Days)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set consists of all randomized subjects who received at least one dose of trial medication.
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
Overall Number of Participants Analyzed 416 423
Measure Type: Number
Unit of Measure: participants
Myocardial infarctions 5 6
Strokes 3 3
Time Frame Adverse Events were collected during the course of the study from Study Day 0 up to Study Day 196.
Adverse Event Reporting Description Adverse Events refer to the Safety Set. Safety Set consists of all subjects who have completed the study or terminated prematurely and who have received at least 1 dose of study medication.
 
Arm/Group Title Alprostadil Placebo
Hide Arm/Group 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.

Alprostadil: - Active Substance: Prostaglandin E1

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion

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.

Placebo: - Active Substance: Lactose

  • Pharmaceutical Form: solution for infusion
  • Concentration: 40 μg b.d.
  • Route of Administration: intravenous infusion
All-Cause Mortality
Alprostadil Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Alprostadil Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   87/416 (20.91%)      62/423 (14.66%)    
Blood and lymphatic system disorders     
ANAEMIA * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
Cardiac disorders     
ACUTE MYOCARDIAL INFARCTION * 1  3/416 (0.72%)  3 3/423 (0.71%)  3
CARDIAC FAILURE * 1  3/416 (0.72%)  3 1/423 (0.24%)  1
ANGINA PECTORIS * 1  2/416 (0.48%)  2 0/423 (0.00%)  0
ATRIAL FIBRILLATION * 1  2/416 (0.48%)  2 1/423 (0.24%)  1
CARDIAC FAILURE ACUTE * 1  2/416 (0.48%)  2 4/423 (0.95%)  4
MYOCARDIAL INFARCTION * 1  2/416 (0.48%)  2 3/423 (0.71%)  3
ATRIOVENTRICULAR BLOCK COMPLETE * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
CARDIOPULMONARY FAILURE * 1  1/416 (0.24%)  1 1/423 (0.24%)  1
MYOCARDIAL ISCHAEMIA * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
VENTRICULAR FIBRILLATION * 1  1/416 (0.24%)  1 1/423 (0.24%)  1
ACUTE CORONARY SYNDROME * 1  0/416 (0.00%)  0 2/423 (0.47%)  2
ACUTE RIGHT VENTRICULAR FAILURE * 1  0/416 (0.00%)  0 1/423 (0.24%)  2
CARDIAC FAILURE CHRONIC * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
NODAL ARRHYTHMIA * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
Gastrointestinal disorders     
DUODENAL ULCER * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
GASTRIC ULCER HAEMORRHAGE * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
INTESTINAL HAEMORRHAGE * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
PANCREATITIS ACUTE * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
MESENTERIC ARTERY EMBOLISM * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
General disorders     
ISCHAEMIC ULCER * 1  2/416 (0.48%)  2 0/423 (0.00%)  0
NECROSIS * 1  2/416 (0.48%)  2 0/423 (0.00%)  0
SUDDEN DEATH * 1  2/416 (0.48%)  2 0/423 (0.00%)  0
DEATH * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
IMPAIRED HEALING * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
MULTI-ORGAN FAILURE * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
PAIN * 1  1/416 (0.24%)  1 3/423 (0.71%)  3
PYREXIA * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
CHEST PAIN * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
WOUND NECROSIS * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
Hepatobiliary disorders     
CHOLELITHIASIS * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
Infections and infestations     
GANGRENE * 1  14/416 (3.37%)  14 11/423 (2.60%)  12
BRONCHOPNEUMONIA * 1  3/416 (0.72%)  3 0/423 (0.00%)  0
CELLULITIS * 1  3/416 (0.72%)  3 3/423 (0.71%)  3
PNEUMONIA * 1  3/416 (0.72%)  3 2/423 (0.47%)  2
INFECTED SKIN ULCER * 1  2/416 (0.48%)  2 1/423 (0.24%)  1
PURULENT DISCHARGE * 1  2/416 (0.48%)  2 0/423 (0.00%)  0
SEPSIS * 1  2/416 (0.48%)  2 1/423 (0.24%)  1
OSTEOMYELITIS * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
POSTOPERATIVE WOUND INFECTION * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
WOUND INFECTION STAPHYLOCOCCAL * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
ABSCESS LIMB * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
ARTHRITIS BACTERIAL * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
LOBAR PNEUMONIA * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
LOCALISED INFECTION * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
Injury, poisoning and procedural complications     
LIMB TRAUMATIC AMPUTATION * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
SHUNT THROMBOSIS * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
JAW FRACTURE * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
WOUND DEHISCENCE * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
Metabolism and nutrition disorders     
DEHYDRATION * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
HYPERKALAEMIA * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
DIABETES MELLITUS * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
Musculoskeletal and connective tissue disorders     
PAIN IN EXTREMITY * 1  2/416 (0.48%)  2 1/423 (0.24%)  1
BURSITIS * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
TENOSYNOVITIS * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
HYPOPHARYNGEAL CANCER STAGE III * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
LUNG NEOPLASM * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
Nervous system disorders     
ISCHAEMIC STROKE * 1  2/416 (0.48%)  2 2/423 (0.47%)  2
CEREBROVASCULAR ACCIDENT * 1  1/416 (0.24%)  1 1/423 (0.24%)  1
DIABETIC COMA * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
SYNCOPE * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
CAROTID ARTERY STENOSIS * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
CEREBROVASCULAR INSUFFICIENCY * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
CONVULSION * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
PSYCHOMOTOR HYPERACTIVITY * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
TRANSIENT ISCHAEMIC ATTACK * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
Respiratory, thoracic and mediastinal disorders     
HYDROTHORAX * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
PULMONARY ARTERY THROMBOSIS * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
PULMONARY EMBOLISM * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
Skin and subcutaneous tissue disorders     
SKIN ULCER * 1  4/416 (0.96%)  4 5/423 (1.18%)  5
DRY GANGRENE * 1  2/416 (0.48%)  2 0/423 (0.00%)  0
SKIN NECROSIS * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
Vascular disorders     
PERIPHERAL ISCHAEMIA * 1  11/416 (2.64%)  14 9/423 (2.13%)  9
EXTREMITY NECROSIS * 1  10/416 (2.40%)  11 9/423 (2.13%)  9
NECROSIS ISCHAEMIC * 1  6/416 (1.44%)  6 0/423 (0.00%)  0
CIRCULATORY COLLAPSE * 1  2/416 (0.48%)  2 0/423 (0.00%)  0
ARTERIAL THROMBOSIS LIMB * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
HYPERTENSION * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
HYPERTENSIVE CRISIS * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
ISCHAEMIA * 1  1/416 (0.24%)  1 1/423 (0.24%)  1
VENOUS THROMBOSIS LIMB * 1  1/416 (0.24%)  1 0/423 (0.00%)  0
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
THROMBOPHLEBITIS * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
THROMBOSIS * 1  0/416 (0.00%)  0 1/423 (0.24%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alprostadil Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   61/416 (14.66%)      62/423 (14.66%)    
Skin and subcutaneous tissue disorders     
SKIN ULCER * 1  24/416 (5.77%)  29 26/423 (6.15%)  28
Vascular disorders     
PERIPHERAL ISCHAEMIA * 1  40/416 (9.62%)  41 41/423 (9.69%)  45
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: UCB Clinical Trial Call Center
Organization: UCB
Phone: +1 877 822 9493 (UCB)
Layout table for additonal information
Responsible Party: UCB Pharma ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier: NCT00596752    
Other Study ID Numbers: SP0777
2005-001970-29 ( EudraCT Number )
First Submitted: December 21, 2007
First Posted: January 17, 2008
Results First Submitted: May 5, 2014
Results First Posted: August 12, 2014
Last Update Posted: April 4, 2018