Prostaglandin E1 in Outpatients With Intermittent Claudication
Condition: Stage II Peripheral Arterial Occlusive Disease; Intermittent Claudication Fontaine Stage II PAOD
MeSH terms: Intermittent Claudication; Arterial Occlusive Diseases
Intervention: Alprostadil (Prostaglandin E1); Pentoxifylline; Placebo to Pentoxifylline oral; Placebo to Alprostadil (Prostaglandin E1) intravenous
Intervention description: 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.; 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.; 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.; 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.
Intervention MeSH terms: Pentoxifylline; Alprostadil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 561.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Alprostadil; Prostaglandin E1; Prostavasin®; PAOD

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.
    

Eligibility 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