Prostaglandin E1 in Outpatients With Intermittent Claudication

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB, Inc.
ClinicalTrials.gov Identifier:
NCT01263925
First received: December 17, 2010
Last updated: May 25, 2012
Last verified: May 2012
  Purpose

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 Intervention 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 Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Intravenous Prostaglandin E1 Treatment in Outpatients With Intermittent Claudication

Resource links provided by NLM:


Further study details as provided by UCB, Inc.:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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:
  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]

    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.


  • 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) ] [ Designated as safety issue: No ]

    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.



Enrollment: 561
Study Start Date: April 2001
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01263925

Locations
Germany
Aachen, Germany
Bad Säckingen, Germany
Berlin, Germany
Bottrop, Germany
Dortmund, Germany
Dresden, Germany
Düsseldorf, Germany
Essen, Germany
Essen-Steele, 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, Germany
Mannheim-Lindenhof, 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, Inc.
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

Additional Information:
No publications provided

Responsible Party: UCB, Inc.
ClinicalTrials.gov Identifier: NCT01263925     History of Changes
Other Study ID Numbers: SP580
Study First Received: December 17, 2010
Results First Received: April 17, 2012
Last Updated: May 25, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by UCB, Inc.:
Alprostadil
Prostaglandin E1
Prostavasin®
PAOD

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Intermittent Claudication
Peripheral Arterial Disease
Vascular Diseases
Cardiovascular Diseases
Arteriosclerosis
Signs and Symptoms
Atherosclerosis
Peripheral Vascular Diseases
Alprostadil
Pentoxifylline
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Free Radical Scavengers
Antioxidants

ClinicalTrials.gov processed this record on April 15, 2014