Peripheral Arterial Occlusive DiseasePhase 4ESPECIALNCT00596752
Alprostadil in Peripheral Arterial Occlusive Disease (PAOD) Stage IV
A Phase 4 study testing Alprostadil in people with Peripheral Arterial Occlusive Disease, run by UCB BIOSCIENCES GmbH at 78 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Peripheral Arterial Occlusive Disease
- What is being tested?
- Alprostadil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 840 participants
- Where
- 78 sitesin 6 countries
- Study dates
- Mar 2004to Jul 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
78 sites in 6 countries.
78 sites in 6 countries
Russia39 sites
246
Barnaul
205
Chelyabinsk
244
Chelyabinsk
228
Irkutsk
242
Kazan'
227
Kemerovo
201
Moscow
202
Moscow
203
Moscow
209
Moscow
219
Moscow
220
Moscow
230
Moscow
248
Moscow
231
Novosibirsk
232
Novosibirsk
222
Omsk
217
Petrozavodsk
206
Rostov-on-Don
225
Rostov-on-Don
236
Rostov-on-Don
239
Rostov-on-Don
224
Ryazan
210
Saint Petersburg
212
Saint Petersburg
213
Saint Petersburg
214
Saint Petersburg
215
Saint Petersburg
216
Saint Petersburg
218
Samara
237
Saratov
243
Tula
234
Tver'
238
Tyumen
241
Ufa
240
Volgograd
221
Yaroslavl
223
Yekaterinburg
247
Yekaterinburg
Ukraine17 sites
112
Dnipropetrovsk
109
Donetsk
110
Donetsk
114
Ivano-Frankivsk
111
Kharkiv
101
Kiev
102
Kiev
103
Kiev
104
Kiev
105
Kiev
106
Lviv
118
Odesa
119
Odesa
113
Uzhhorod
116
Vinnytsia
107
Zaporizhzhya
108
Zaporizhzhya
Poland16 sites
306
Bydgoszcz
321
Gmina Końskie
320
Krakow
314
Lublin
315
Lublin
316
Poznan
317
Poznan
301
Szczecin
304
Szczecin
307
Warsaw
308
Warsaw
309
Warsaw
318
Warsaw
319
Warsaw
312
Wroclaw
322
Zamość
About this study
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)
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.
- Conditions
- Peripheral Arterial Occlusive Disease
- Being tested
- Alprostadil, Placebo
- Keywords
- Alprostadil, Prostavasin, PAOD, Fontaine Stage IV
- Medical subject headings
- Peripheral Arterial Occlusive Disease 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlprostadilDrug
Also called Prostavasin
- Active Substance: Prostaglandin E1
- Pharmaceutical Form: solution for infusion
- Concentration: 40 μg b.d.
- Route of Administration: intravenous infusion
PlaceboOther
- Active Substance: Lactose
- Pharmaceutical Form: solution for infusion
- Concentration: 40 μg b.d.
- Route of Administration: intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Alprostadil | Experimental | 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. Receives: Drug: Alprostadil |
| Placebo | Placebo comparator | 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 12 weeks after the end of study drug treatment
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.
Measured: At 24 weeks after the end of study drug treatment
Secondary outcomes (10)
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.
Measured: At 24 weeks after the end of study drug treatment
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.
Measured: At 24 weeks after the end of study drug treatment
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 %.
Measured: At 24 weeks after the end of study drug treatment
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.
Measured: During the course of the study (up to 196 days)
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.
Measured: At 24 weeks after the end of study drug treatment
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.
Measured: At 24 weeks after the end of study drug treatment
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.
Measured: At 24 weeks after the end of study drug treatment
All-cause Mortality During the Course of the Study (up to 196 Days)
Measured: During the course of the study (up to 196 days)
Cardiovascular Mortality During the Course of the Study (up to 196 Days)
Measured: 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.
Measured: During the course of the study (up to 196 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2008 (estimated)
- Study startMar 2004
- Primary completionMay 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral Arterial Occlusive DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 840 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCB BIOSCIENCES GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Aptiv Solutions
- Responsible party
- Sponsor
- Investigators
- UCB Clinical Trial Call Center, Study director, +1 877 822 9493 (UCB)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00596752
- Sponsor's protocol ID
- SP0777
- Other IDs
- 2005-001970-29, 2005
- Acronym
- ESPECIAL
- Status last verified
- Mar 2018
- First submitted
- 21 Dec 2007
- Last updated
- 4 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 28189475
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00596752
- Acronym / sponsor ID
- ESPECIAL / SP0777
- Conditions
- Peripheral Arterial Occlusive Disease
- Keywords
- Alprostadil, Prostavasin, PAOD, Fontaine Stage IV
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 840 participants (actual)
- Lead sponsor
- UCB BIOSCIENCES GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Aptiv Solutions
- Study start
- Mar 2004
- Primary completion
- May 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 17 Jan 2008 (estimated)
- Results
- Posted 12 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alprostadil | Experimental | Drug: AlprostadilProstavasin® 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 | Placebo comparator | Other: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlprostadilAlso: Prostavasin* Active Substance: Prostaglandin E1 * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion | Drug | Alprostadil |
| Placebo* Active Substance: Lactose * Pharmaceutical Form: solution for infusion * Concentration: 40 μg b.d. * Route of Administration: intravenous infusion | Other | Placebo |
Primary outcome
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
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
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.
10 secondary outcomes
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
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
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
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)
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
Minor Amputations at 24 Weeks After the End of Study Drug Treatment
Time frame: At 24 weeks after the end of study drug treatment
Revascularization Procedures at 24 Weeks After the End of Study Drug Treatment
Time frame: At 24 weeks after the end of study drug treatment
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)
Cardiovascular Mortality During the Course of the Study (up to 196 Days)
Time frame: During the course of the study (up to 196 days)
Cardiovascular Morbidity During the Course of the Study (up to 196 Days)
Time frame: During the course of the study (up to 196 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28189475Lawall 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.
- FDA Safety Alerts and RecallsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
UCB Clinical Trial Call Center study director
+1 877 822 9493 (UCB)
78 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alprostadil in people with Peripheral Arterial Occlusive Disease, run by UCB BIOSCIENCES GmbH at 78 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 78 sites in Russia, Ukraine, Poland, Mexico, Czechia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00596752, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2018.