Methods

Study design: States randomized, double‐blinded.

Method of randomization: Not stated.

Blinding: Double‐blinded.

Dropouts: 2 patients from the buflomedil group, because they felt better, and 4 from the placebo group; 1 for no apparent reason, 1 fatal AMI, 1 underwent surgery and 1 failed to report.

Participants

Country: Greece.

Setting: Clinic.

No. 40 patients; 21 buflomedil, 19 placebo).

Gender: 36 males (19 buflomedil, 17 placebo), 4 females (2 bufomedil, 2 placebo).

Age: mean 60.1 years (range 39 to 77).

Inclusion criteria: All had maturity onset diabetes mellitus (11 insulin‐dependent,
29 non‐insulin dependent, mean duration 14 years) mean duration PAOD 3.4 years, walking distance < 400 m. SBP indices at both ankles estimated by Doppler.

At the start of a 4‐week observation period before entry into the study, patients were given a full physical examination and an ECG at rest and after exercise on a treadmill (3.6 km/h at 12.5°C).

Exclusion criteria: Vascular surgery or specific physical training, participation in another study, history of cerebrovascular accident or coronary heart disease, concomitant therapy that could influence any of the parameters to be studied, evidence of excessive Monckeberg's sclerosis, diabetic retinopathy, severe renal, hepatic or cardiopulmonary impairment, uncontrolled arterial hypertension, previous AMI, angina pectoris, severe cardiac arrhythmias, evidence of peripheral sensory neuropathy, arterial bleeding, pregnancy or lactation, allergy to any medication, history of convulsions or other central nervous system diseases, grossly over‐ or under‐weight diabetics based on tables size‐weight, musculoskeletal disorders limiting walking ability.

Interventions

Treatment: During 6 month treatment period patients received 600 mg buflomedil per day, 2 x 150 mg tablets taken twice a day.

Control: Matching placebo tablets.

Compliance checked every 3 to 4 weeks by patients returning their bottles to the outpatient clinic where remaining tablets were counted.

Duration: Six months.

Outcomes

Primary: Distances at 6 months constituted the primary response variables. PFWD and MWD measured at entry (baseline) and after 3 and 6 months' treatment using a standardized exercise test on the treadmill (3.6 km/h at 12.5°C).

Secondary: Not stated.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear

Methods

Study design: States randomized, double‐blinded.

Method of randomization: Not stated.

Blinding: Double‐blinded.

Dropouts: 8 in the placebo group and 12 in the buflomedil group, leaving 93 for analysis (46 in placebo group, 47 in buflomedil group).

Participants

Country: Germany.

Setting: Clinic.

No.: 113 patients.

Age: 50 to 70 years old.

Gender: Not stated.

Inclusion criteria: Symptoms of intermittent claudication for 6 months to 5 years and PFWD of 50 to 400 m.

After a four‐week run‐in period during which all patients received placebo and other vasoactive drugs were stopped, patients were checked to test whether their PFWD differed by not more than 30% from the value at the beginning of the run‐in period (mean of two consecutive measurements). Patients were then allocated randomly to treatment groups.

Exclusion criteria: Special physical training for at least six months prior to study start; systolic blood pressure at the ankle og less than 70 mmHg, diabetic microangiopathy or necrosis, infalmmatory vascular disease such as endarteritis obliterans, coronoary heart disease with angina pectoris, myocardial insufficiency, respiratory insufficiency, arthropathy, symptoms of severe liver or kidney disease, laboratory values of more than 10% outside normal range, pregnancy, beta‐blockers and any other vasoactive drugs.

Interventions

All patients received placebo tablets (four daily ‐ 2 in the morning, one at midday and one in the evening) for four weeks run‐in.

Treatment: Buflomedil 600 mg daily (2 x 150 mg in the morning, 1 x 150 mg at midday and 1 x 150mg in the evening.)

Control: Matching placebo.

Duration: 12 weeks treatment.
(16 weeks in total including the 4 week run‐in period.)

Outcomes

Primary: PFWD and MWD were measured by treadmill (5 km/h at 10° elevation).

Ankle‐arm pressures were measured by Doppler at rest and after exercise and pressure differences (brachial artery‐posterior tibial artery) were calculated.

Measurements were performed at days 28, 56, and 84.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B ‐ Unclear