Bishop 1992.
Methods | Randomised controlled trial (2 centres) conducted in the USA | |
Participants | 93 participants randomly assigned, with venous stasis ulcers 3 cm2 to 50 cm2 in size, of at least 3 months' duration Group 1: 30 participants Group 2: 31 participants Group 3: 32 participants Mean baseline ulcer size of completers, cm2 ± SD (median): Group 1: 9.6 ± 8.1 (6.2) Group 2: 11.9 ± 11.2 (6.9) Group 3: 9.9 ± 8.5 (6.5) Mean baseline ulcer duration of completers, months ± SD (median): Group 1: n = 29, 38.0 ± 88.7 (12.0) Group 2: n = 28, 44.1 ± 58.0 (19.0) Group 3: n = 29, 57.1 ± 94.9 (11.0) Patients with > 105 bacteria/gram ulcer tissue (confirmed by tissue biopsy) were excluded, as were those with systemic sepsis or bone infection |
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Interventions | Group 1: Placebo (topical preparation comprising petroleum‐based cream, vehicle of preparation used for Group 3) Group 2: Topical preparation comprising 1% silver sulphadiazine cream Group 3: Topical preparation comprising 0.4% tripeptide copper complex cream All participants received ulcer cleansing with normal saline and compression; and were instructed to apply treatment daily followed by nonadherent dressing and elastic wrap, and to keep the affected limb elevated when sitting. The treatment duration was 4 weeks |
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Outcomes | Numbers (%) of participants with ulcers healed at week 4: Group 1: 1/30 (3) Group 2: 6/31 (19) Group 3: 0/32 (0) Numbers (%) of participants whose ulcers remained healed after 1 year, having received no further topical treatment, just elastic support: Group 1: 1/1 (100) Group 2: 5/6 (83) Group 3: 0/0 (0) Mean percentage change in ulcer size % ± SE at week 4: Group 1: ‐22.5 ± 10.2 Group 2: ‐44.0 ± 8.21 Group 3; ‐18.7 ± 9.07 Secondary outcomes: No microbiological outcomes reported Adverse events: The trial authors reported no statistically significant between‐group differences for burning, itching, pain or oedema observed (numbers of participants and P values not provided). Only placebo group complained of pain, itching or burning after 15 days. On a scale of 0 to 3+, all mean scores were less than 1+ (direction and administration of scale not explained) |
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Notes | Withdrawals Group 1: 1/30 (3%) Group 2: 3/31 (10%) (2 were immediate withdrawals) Group 3: 3/32 (9%) (1 was an immediate withdrawal) Apart from the information about immediate withdrawals, other information, including reasons for withdrawal, was not provided |
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Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Unclear risk | "Patients...were stratified by lesion size and randomly assigned to one of three treatment groups". No information regarding sequence generation reported |
Allocation concealment (selection bias) | Unclear risk | "Patients meeting the inclusion criteria and completing an informed consent form were stratified by lesion size and randomly assigned to one of three treatment groups". No information regarding allocation concealment reported |
Blinding (performance bias and detection bias) Participant blinded to the intervention | Unclear risk | No information regarding blinding of participants reported |
Blinding (performance bias and detection bias) Outcome assessor blinded to the intervention | Low risk | "Before evaluation, all medication was removed and the ulcer cleaned to keep the evaluator blinded" |
Incomplete outcome data (attrition bias) Drop out rate described | Unclear risk | Numbers of withdrawals reported per treatment arm but reasons not provided |
Incomplete outcome data (attrition bias) Drop out rate acceptable | Low risk | Withdrawals: Group 1: 1/30 (3%) Group 2: 3/31 (10%) Group 1: 3/32 (9%) Overall withdrawal rate 8%; 86/93 (92%) completed the study |
Incomplete outcome data (attrition bias) ITT analysis | Unclear risk | Per protocol, "eighty‐six were evaluable for efficacy". It is unclear how these withdrawals might have impacted estimates of treatment effect (this is a small RCT) |
Baseline factors comparable | High risk | On the basis of median values, Group 2 (1% silver sulphadiazine) included participants with longer ulcer duration, on average, than the other groups. Treatment groups appear comparable in terms of ulcer area |