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. 2014 Jan 10;2014(1):CD003557. doi: 10.1002/14651858.CD003557.pub5

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
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
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)
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
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