Alprostadil in Peripheral Arterial Occlusive Disease (PAOD) Stage IV

Peripheral Arterial Occlusive Disease Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00596752
• Other study ID #: SP0777
• Secondary ID: 2005-001970-29
• Status: Completed
• Phase: Phase 4
• First received: December 21, 2007
• Last updated: March 8, 2018
• Start date: March 2004
• Est. completion date: July 2013

Study information

• Verified date: March 2018
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 840
• Est. completion date: July 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arterial Occlusive Diseases
• Peripheral Arterial Disease
• Peripheral Arterial Occlusive Disease

Intervention

Drug:
• Alprostadil
Active Substance: Prostaglandin E1 Pharmaceutical Form: solution for infusion Concentration: 40 µg b.d. Route of Administration: intravenous infusion

Other:
• Placebo
Active Substance: Lactose Pharmaceutical Form: solution for infusion Concentration: 40 µg b.d. Route of Administration: intravenous infusion

Locations

Country	Name	City	State
Czechia	404	Plzen
Czechia	414	Usti Nad Labem
Germany	1	Karlsbad
Mexico	502	Aguascalientes
Mexico	505	Merida
Mexico	501	Queretaro
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
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	209	Moscow
Russian Federation	219	Moscow
Russian Federation	220	Moscow
Russian Federation	230	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	210	St Petersburg
Russian Federation	212	St Petersburg
Russian Federation	213	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
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

Sponsors (2)

Lead Sponsor	Collaborator
UCB BIOSCIENCES GmbH	Aptiv Solutions

Countries where clinical trial is conducted

Czechia,  Germany,  Mexico,  Poland,  Russian Federation,  Ukraine, 

References & Publications (1)

Lawall H, Pokrovsky A, Checinski P, Ratushnyuk A, Hamm G, Randerath O, Grieger F, Bentz JW. Efficacy and Safety of Alprostadil in Patients with Peripheral Arterial Occlusive Disease Fontaine Stage IV: Results of a Placebo Controlled Randomised Multicentre — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At 12 weeks after the end of study drug treatment
Primary	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.	At 24 weeks after the end of study drug treatment
Secondary	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.	At 24 weeks after the end of study drug treatment
Secondary	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.	At 24 weeks after the end of study drug treatment
Secondary	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 %.	At 24 weeks after the end of study drug treatment
Secondary	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.	During the course of the study (up to 196 days)
Secondary	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.	At 24 weeks after the end of study drug treatment
Secondary	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.	At 24 weeks after the end of study drug treatment
Secondary	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.	At 24 weeks after the end of study drug treatment
Secondary	All-cause Mortality During the Course of the Study (up to 196 Days)		During the course of the study (up to 196 days)
Secondary	Cardiovascular Mortality During the Course of the Study (up to 196 Days)		During the course of the study (up to 196 days)
Secondary	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.	During the course of the study (up to 196 days)

External Links

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