Ketanserin therapy: randomised trials

TrialApelqvist et al, 1990Martinez-de Jesus et al, 1997Janssen et al, unpublished
Treatment comparison(s)T1: Oral ketanserin
T2: Placebo
T1: Topical ketanserin (2%) ointment
T2: Placebo (unmatched, saline)
T1: Topical ketanserin (2%) ointment
T2: Placebo (matched)
Other featuresAll patients received a 2-week placebo run in. Check-up visits occurred at monthly intervals. Antibiotics were used in response to infection, footwear was corrected and surgical debridement provided where required.
T1: Oral ketanserin (20 mg 3 times daily for 1 month then 40 mg 3 times daily for 2 months).
All patients were hospitalised for debridement, systemic antibiotic treatment, foot rest and correction of fasting hyperglycaemia caused by sepsis. Patients received outpatient care after discharge.T1: Ketanserin (2%) ointment was administered twice daily.
All patients received conventional wound care, surgical debridement of necrotic tissue and mechanical debridement of necrotic tissue and exudate with saline impregnated gauze.
Of 299 patients randomised, only 45 were diabetic patients.
LocationSwedenMexicoMulticentre, Germany
Baseline comparability at p>0.05Yes, except hypertension more common in ketanserin group p<0.05 and systolic arm pressure lower in ketanserin group p<0.05Yes, except smoking: more common in the ketanserin group (p=0.043).Yes
Blinding levelDouble blind (patient and investigator)Single blinded (patient)Double blind (patient and investigator)
Concealment of allocationNot reportedNo, sequential allocationNot recorded
Inclusion/exclusionInclusion: Diabetic patients with deep or superficial foot ulcers, area 1 cm2, systolic toe pressure below 45 mmHg.
Exclusion: Severe liver or kidney insufficiency; myocardial infarction within 3 months, congestive heart disease (NYHA III–IV), treatment with β-Blocker, unable to co-operate.
Inclusion: NIDDM patients with neurotrophic, non-healing foot ulcers (Wagner grade II or III).
Exclusion: Metabolic instability at discharge.
Inclusion: Patients with chronic skin ulcers: decubitus (80), venous insufficiency (134), inoperable arterial and arteriolar ulcers (40) and diabetic foot ulcers (45).
Exclusion: Patients with a life expectancy of less than 6 months
Numbers randomisedT1: 20; T2: 20Total: 161T1: 150; T2: 149
Length of follow-up3 months12 weeks8 weeks
Loss to follow-up (%)5 lost in run-in period, and not included in numbers randomised21 withdrew by 2 weeks and are not included in analysisNot recorded
Type of analysisEndpoint analysisEndpoint analysisEndpoint analysis
Outcomes/endpointsUlcer healed:
T1: 7/20 (35%); T2: 5/20 (25%)
Improved (wound size decreased by 50% or more):
T1: 4/20 (20%); T2: 2/20 (10%)
No improvement/deterioration:
T1: 6/20 (30%); T2: 6/20 (30%)
Gangrene (*amputated):
T1: 2/20 (10%) (2*); T2: 6/20 (30%) (4*)
T1: 1/20 (5%); T2: 1/20 (5%)
No comparisons gave statistically significant differences.
Mean reduction in ulcer area(%):
T1: 87%; T2: 62.8%; p<0.001
Average daily reductions in ulcer area (mm2/day):
T1: 4.5; T2: 2.88
No adverse effects were detected.
Subgroup analysis of 45 diabetic patients:
Increase in initial healing velocity relative to placebo:
ketanserin showed 2.96 fold increase (196% faster) (p<0.001).
Comparability of diabetic patients at baseline is unknown. Across all patient groups, ketanserin showed no increase in side-effects above placebo treatment.
Economic data

From: Appendix 13, Ketanserin therapy

Cover of Clinical Guidelines for Type 2 Diabetes
Clinical Guidelines for Type 2 Diabetes: Prevention and Management of Foot Problems [Internet].
NICE Clinical Guidelines, No. 10.
School of Health and Related Research (ScHARR), University of Sheffield.
Sheffield (UK): University of Sheffield; 2003.
Copyright © 2003, School of Health and Related Research (ScHARR), University of Sheffield.

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