Smith 1992.

Methods	Randomised controlled trial conducted in the UK
Participants	200 people with venous leg ulcers (ABPI ≥ 0.75) ≥ 2 cm in diameter were recruited. Those with the following were excluded: diabetes; rheumatoid arthritis; infected ulcers requiring treatment that precluded dressings being left in situ; infection requiring immediate antibiotics; known intolerance to iodine; and neurological disease causing tropic impairment Group 1: 99 Group 2: 101 Participants with smaller baseline ulcer diameter (2 to 4 cm) Group 1a: 64 Group 2a: 62 Participants with larger baseline ulcer diameter > 4 cm Group 1b: 35 Group 2b: 39 Median (interquartile range) baseline ulcer area (cm2) in participants with smaller/larger ulcers: Group 1: 3.1 (2.0 to 5.0)/13.3 (9.0 to 27.0); Group 2: 2.6 (2.0 to 4.0)/17.6 (9.0 to 38.0) Median (interquartile range) baseline ulcer duration (months) in participants with smaller/larger ulcers: Group 1: 5 (3 to 9)/14 (2 to 45); Group 2: 3 (2 to 10)/17 (6 to 58) Ulcers were not clinically infected at baseline. Most had bacteria present at initial assessment
Interventions	1. Ulcers cleansed with sterile isotonic saline and ulcers filled with hydrocolloid powder (Biofilm powder) until level with the ulcer margins, before a hydrocolloid dressing (Biofilm dressing) was applied. Participants were allowed to remove their compression bandages and bathe or shower with the dressing in place 2. Ulcers cleansed with sterile isotonic saline, then povidone‐iodine dressing applied (Betadine), cut to fit exactly the shape of the ulcer, and an absorbent pad placed over. Participants could not bathe or shower with the dressing in place All participants were treated in a community setting and received graduated compression in the form of an elasticated tubular bandage (2 layers of shaped Tubigrip) or a stocking (Venosan 2002)
Outcomes	Frequency of complete healing at 4 months: 1a: 38/64 (59%) 2a: 43/62 (69%) P value 0.27 1b: 12/35 (34%) 2b: 4/39 (10%) P value 0.02 (reported by trial authors) Cox proportional hazards model found that the following 4 variables were significant independent predictors of time to healing (P value < 0.01): baseline ulcer area, ulcer duration, age, deep vein involvement. No significant interaction was detected between treatment and baseline ulcer area. Hazard ratio estimate of treatment effect not reported Median (interquartile range) healing rate (cm²/d) at 1 month (analysis based on 151 participants): 1a(50 participants analysed): 0.056 (0.027 to 0.085) 2a (52 participants analysed): 0.062 (0.039 to 0.086) P value 0.40 Mann‐Whitney U‐test 1b (25 participants analysed): 0.184 (0.115 to 0.338) 2b (24 participants analysed): 0.017 (0.001 to 0.267) P value 0.09 Mann‐Whitney U‐test Numbers (%) of participants reporting moderate or severe ulcer pain, assessed using 5‐point scale (1 = no pain and 5 = worst pain) at 1 month (analysis based on 123 participants): 1a: 6/34 (18%) 2a: 16/36 (44%) P value 0.02 1b: 12/27 (44%) 2b: 14/26 (54%) P value 0.02 Estimated cost of dressings and nursing time over 4 months (GBP, price year not stated, analysis based on all 200 participants): Participants with smaller wounds, defined as baseline diameter < 6 cm: 1a: 48.96 2a: 38.95 Participants with large wounds, defined as baseline diameter ≥ 6 cm: 1b: 526.63 2b: 183.75
Notes	In participants with bilateral ulceration, the right leg was included as the study limb Numbers of participants (%) who withdrew, with reasons: Group 1: total = 27/99 (27%) Refused treatment (12); acute infection (1); admission (7); allergy (6); moved (1) Group 2: total = 33/101 (33%) Refused treatment (11); acute infection (12); admission (5); allergy (2); died (2); moved (1)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"200 patients with VLUs assessed by continuous wave ultrasound and plethysmography were randomly allocated to each treatment group, stratified by initial maximum ulcer diameter 2‐4 cm and >4 cm, using a block length of 4 within each strata." It was not stated how the sequence was generated
Allocation concealment (selection bias)	Unclear risk	No information provided
Blinding (performance bias and detection bias) Participant blinded to the intervention	High risk	"this was not a blind study"
Blinding (performance bias and detection bias) Outcome assessor blinded to the intervention	High risk	"this was not a blind study"
Incomplete outcome data (attrition bias) Drop out rate described	Low risk	Dropout rate described (60/200 participants)
Incomplete outcome data (attrition bias) Drop out rate acceptable	High risk	"70% completed the trial"
Incomplete outcome data (attrition bias) ITT analysis	High risk	"Five patients did not receive their randomly allocated treatment because of clerical errors. Two patients received biofilm instead of Betadine and three patients received Betadine instead of biofilm. Statistical analysis was performed on basis of treatment received"
Baseline factors comparable	High risk	Of those with larger ulcers at baseline (> 4 cm diameter), Group 2 included more participants with larger ulcers and wounds of longer duration