Prostaglandin E1 in Outpatients With Intermittent Claudication

• ClinicalTrials.gov Identifier: NCT01263925
• Recruitment Status: Completed
• First Posted: December 21, 2010
• Results First Posted: June 29, 2012
• Last Update Posted: October 27, 2014
• Sponsor: UCB Pharma
• Information provided by (Responsible Party): UCB Pharma

Study Description

Brief Summary:

Investigate, under outpatient conditions, both the effect of 4 weeks of daily treatment with Prostaglandin E1 and that of 4 weeks of interval treatment (two infusions per week) on the pain-free walking distance in patients with Intermittent Claudication.

Condition or disease	Intervention/treatment	Phase
Stage II Peripheral Arterial Occlusive Disease; Intermittent Claudication Fontaine Stage II PAOD	Drug: Alprostadil (Prostaglandin E1); Drug: Pentoxifylline; Drug: Placebo to Pentoxifylline oral; Drug: Placebo to Alprostadil (Prostaglandin E1) intravenous	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 561 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Intravenous Prostaglandin E1 Treatment in Outpatients With Intermittent Claudication
• Study Start Date: April 2001
• Actual Primary Completion Date: April 2011
• Actual Study Completion Date: April 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Alprostadil; Alprostadil (Prostaglandin E1) intravenous and matching Placebo to Pentoxifylline oral	Drug: Alprostadil (Prostaglandin E1); 4-week Daily Treatment Period 1: 4 weeks of 1 x daily intravenous infusion of 3 ampoules (20 µg) of Prostaglandin E1 (total 60 µg) in 50 - 250 ml physiological saline solution over 2 hours. 4-week Interval Treatment Period 2: 4 weeks of 2 x weekly intravenous infusion of 3 ampoules (20 µg) of Prostaglandin E1 (total 60 µg) in 50 - 250 ml physiological saline solution over 2 hours.; Other Name: Prostavasin; Drug: Placebo to Pentoxifylline oral; 4-week Daily Treatment Period 1: 4 weeks of 2 x daily (including weekends) matching Placebo to Pentoxifylline tablets. 4-week Interval Treatment Period 2: 4 weeks of 2 x daily (including weekends) matching Placebo to Pentoxifylline tablets.
Active Comparator: Pentoxifylline; Pentoxifylline oral and matching Placebo to Alprostadil (Prostaglandin E1) intravenous	Drug: Pentoxifylline; 4-week Daily Treatment Period 1: 4 weeks of 2 x daily (including weekends) 600 mg Pentoxifylline tablets. 4-week Interval Treatment Period 2: 4 weeks of 2 x daily (including weekends) 600 mg Pentoxifylline tablets.; Other Name: Trental®; Drug: Placebo to Alprostadil (Prostaglandin E1) intravenous; 4-week Daily Treatment Period 1: 4 weeks of 1 x daily intravenous infusion of Placebo in 50 - 250 ml physiological saline solution over 2 hours. 4-week Interval Treatment Period 2: 4 weeks of 2 x weekly intravenous infusion of Placebo in 50 - 250 ml physiological saline solution over 2 hours.

Outcome Measures

Primary Outcome Measures :

1. Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings at Baseline [ Time Frame: From Baseline to the end of 4 weeks of Interval Treatment (Period 2) ]
   The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 2 divided by the pain-free walking distance at Baseline with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
2. Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings at Baseline [ Time Frame: From Baseline to the end of 6-months Follow-up (Period 3) ]
   The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 3 divided by the pain-free walking distance at Baseline with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
3. Ratio of Pain-free Walking Distance After Period 1 in Comparison With the Findings at Baseline [ Time Frame: From Baseline to the end of 4 weeks of Daily Treatment (Period 1) ]
   The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 1 divided by the pain-free walking distance at Baseline with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.

Secondary Outcome Measures :

1. Ratio of Pain-free Walking Distance After Period 2 in Comparison With the Findings After Period 1 [ Time Frame: From the end of 4 weeks of Daily Treatment (Period 1) to the end of 4 weeks of Interval Treatment (Period 2) ]
   The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 2 divided by the pain-free walking distance after Period 1 with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
2. Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 1 [ Time Frame: From the end of 4 weeks of Daily Treatment (Period 1) to the end of 6-months Follow-up (Period 3) ]
   The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 3 divided by the pain-free walking distance after Period 1 with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
3. Ratio of Pain-free Walking Distance After Period 3 in Comparison With the Findings After Period 2 [ Time Frame: From the end of 4 weeks of Interval Treatment (Period 2) to the end of 6-months Follow-up (Period 3) ]
   The ratio of pain-free walking distance was calculated by the pain-free walking distance after Period 3 divided by the pain-free walking distance after Period 2 with determination of pain-free walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
4. Ratio of Maximum Walking Distance After Period 1 in Comparison With the Findings at Baseline [ Time Frame: From Baseline to the end of 4 weeks of Daily Treatment (Period 1) ]
   The ratio of maximum walking distance was calculated by the maximum walking distance after Period 1 divided by the maximum walking distance at Baseline with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
5. Ratio of Maximum Walking Distance After Period 2 in Comparison With the Findings at Baseline [ Time Frame: From Baseline to the end of 4 weeks of Interval Treatment (Period 2) ]
   The ratio of maximum walking distance was calculated by the maximum walking distance after Period 2 divided by the maximum walking distance at Baseline with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
6. Ratio of Maximum Walking Distance After Period 2 in Comparison With the Findings After Period 1 [ Time Frame: From the end of 4 weeks of Daily Treatment (Period 1) to the end of 4 weeks of Interval Treatment (Period 2) ]
   The ratio of maximum walking distance was calculated by the maximum walking distance after Period 2 divided by the maximum walking distance after Period 1 with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
7. Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings at Baseline [ Time Frame: From Baseline to the end of 6-months Follow-up (Period 3) ]
   The ratio of maximum walking distance was calculated by the maximum walking distance after Period 3 divided by the maximum walking distance at Baseline with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
8. Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings After Period 1 [ Time Frame: From the end of 4 weeks of Daily Treatment (Period 1) to the end of 6-months Follow-up (Period 3) ]
   The ratio of maximum walking distance was calculated by the maximum walking distance after Period 3 divided by the maximum walking distance after Period 1 with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
9. Ratio of Maximum Walking Distance After Period 3 in Comparison With the Findings After Period 2 [ Time Frame: From the end of 4 weeks of Interval Treatment (Period 2) to the end of 6-months Follow-up (Period 3) ]
   The ratio of maximum walking distance was calculated by the maximum walking distance after Period 3 divided by the maximum walking distance after Period 2 with determination of maximum walking distances on the treadmill (12 % grade and 3 km/h). If a subject was not familiar with the treadmill, at least two test determinations were performed to accustom him/her to the treadmill. For all treadmill determinations the subject has been prevented from observing the treadmill display of the walking distance achieved.
10. Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 1 [ Time Frame: From Baseline to the end of 4 weeks of Daily Treatment (Period 1) ]

    Scores for subscales were calculated by summing non-missing item scores ranging from 1 (not at all; best possible outcome) to 4 (extremely; worst possible outcome) divided by the number of non-missing items. Hence each subscale score ranges from 1 (best possible outcome) to 4 (worst possible outcome). For subscales 'Mood' and 'Treatment expectation' five items each had to be reversed in order. Additionally, subjects were asked to assess their general health and quality of life on an ordinal scale between 0 (very good) and 10 (very poor).

    Negative changes show a decrease from Baseline.

11. Changes in Quality of Life (as Measured With the PAVK 86 Questionnaire) From Baseline to the End of Period 3 [ Time Frame: From Baseline to the end of 6-months Follow-up (Period 3) ]

    Scores for subscales were calculated by summing non-missing item scores ranging from 1 (not at all; best possible outcome) to 4 (extremely; worst possible outcome) divided by the number of non-missing items. Hence each subscale score ranges from 1 (best possible outcome) to 4 (worst possible outcome). For subscales 'Mood' and 'Treatment expectation' five items each had to be reversed in order. Additionally, subjects were asked to assess their general health and quality of life on an ordinal scale between 0 (very good) and 10 (very poor).

    Negative changes show a decrease from Baseline.

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects with Peripheral Arterial Occlusive Disease (PAOD) of the lower extremity in Fontaine stage II
• Maximum walking distance on the treadmill (12 %, 3 km/h) between 30 and 150 m
• Stable Intermittent Claudication of at least 6 months standing with no acute shortening of walking distance over the past 3 months
• Stenoses or occlusions below the Femoral Bifurcation (above-knee or below-knee type) confirmed by duplex US or angiography
• Ankle/brachial index ≤ 0.90 with a decrease in systolic ankle pressure of ≥ 10 % after maximum loading (maximum walking distance on the treadmill at 3 km/h, 12 %)
• The patient is physically and mentally capable of participating in the trial
• Patient age > 40 years, male and female
• Patient is informed and given ample time and opportunity to think about her/his participation and has given her/his written informed consent
• Patient is willing and able to comply with all trial requirements

Exclusion Criteria:

• Surgical or other interventional measures performed on the affected extremity and Prostaglandin treatment within the 6 months immediately prior to the trial
• Rest pain and Necroses
• Systolic ankle pressure less than 50 mmHg
• Change in maximum walking distance during the one-week Run-in Phase of more than ± 25 % of Baseline
• Successful physical walking training within the 6 months immediately prior to the trial
• Inflammatory vascular diseases
• Polyneuropathy in Diabetes Mellitus
• Diseases limiting walking distance (Arthrosis, inflammatory diseases of the joints, neurological disease, diseases of the Vertebral Column, cardiopulmonary diseases)
• History of Pulmonary Oedema
• Myocardial infarction within the past 6 months
• Pregnancy or nursing
• Known hypersensitivity to any components of the trial medication or comparative drug
• Renal insufficiency, compensated retention (creatinine > 2.0 mg/dL)
• Severe retinal Haemorrhage
• Massive Haemorrhage
• Known existing malignant diseases
• Vasoactive concomitant medication (e.g. Naftidrofuryl, Pentoxifylline, Buflomedil, Cilostazol), or other Prostaglandins
• Untreated or uncontrolled Hypertension (systolic blood pressure ≥ 180 mmHg, diastolic blood pressure ≥ 110 mmHg)
• Previous participation of the patient in the present trial
• Participation of the patient in a trial with the same objectives within the past 6 months, or is currently participating in another trial
• Illness of the patient due to alcohol or drug-abuse within the past 6 months
• Serious illness of the patient that the investigator considers to compromise his/her participation in the trial

Contacts and Locations

Locations

Germany

Aachen, Germany

Bad Säckingen, Germany

Berlin, Germany

Bottrop, Germany

Dortmund, Germany

Dresden, Germany

Düsseldorf, Germany

Essen-Steele, Germany

Essen, Germany

Freiburg, Germany

Gaggenau, Germany

Görlitz, Germany

Hamburg, Germany

Hannover, Germany

Hattingen, Germany

Heidelberg, Germany

Homburg, Germany

Jena, Germany

Karlsbad-Lang Ensteinbach, Germany

Kassel, Germany

Krefeld, Germany

Köln, Germany

Leipzig, Germany

Lüneburg, Germany

Mannheim-Lindenhof, Germany

Mannheim, Germany

Mönchengladbach, Germany

München, Germany

Neuss, Germany

Nürnberg, Germany

Osnabrück, Germany

Papenburg, Germany

Regensburg, Germany

Seesen, Germany

Warendorf, Germany

Wuppertal, Germany

Sponsors and Collaborators

UCB Pharma

Investigators

• Study Director: UCB Clinical Trial Call Center; +1 877 822 9493 (UCB)

More Information

Additional Information:

FDA Safety Alerts and Recalls 

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT01263925
• Other Study ID Numbers: SP0580
• First Posted: December 21, 2010
• Results First Posted: June 29, 2012
• Last Update Posted: October 27, 2014
• Last Verified: May 2012

Keywords provided by UCB Pharma:

Alprostadil; Prostaglandin E1; Prostavasin®; PAOD

Additional relevant MeSH terms:

Intermittent Claudication; Arterial Occlusive Diseases; Arteriosclerosis; Vascular Diseases; Cardiovascular Diseases; Pentoxifylline; Alprostadil; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Radiation-Protective Agents; Protective Agents; Physiological Effects of Drugs; Vasodilator Agents; Free Radical Scavengers; Antioxidants; Urological Agents