McDaniel 2017.

Methods	RCT Setting: clinical research centre associated with large university Country: USA Duration of follow‐up: 8 weeks Treatments: oral EPA + DHA vs placebo; all participants had silver‐coated dressing beneath a 4‐layer compression dressing
Participants	40 participants with VLUs (5 with missing data) Mean age: 60.3 (SD 12.6) years vs 60.9 (SD 11.8) years (EPA + DHA vs placebo) Sex (M:F): 10:6 vs 11:8 (EPA + DHA vs placebo) Stage of ulcer: not reported Ulcer duration: EPA + DHA: < 6 months: 8 participants (50%) and > 6 months: 8 participants (50%); vs placebo: < 6 months: 7 participants (37%) and > 6 months: 12 participants (63%) Ulcer size at baseline: 15.6 (SD 34.4) cm² vs 19.7 (SD 23.2) cm² (EPA + DHA vs placebo) Wound infection: not reported Inclusion criteria: aged 18‐81 years; ≥ 1 existing VLU between the ankle and knee for 3 months; prescribed compression therapy; ABPI of 0.8; target wound ≥ 5 cm² Exclusion criteria: allergic to fish or seafood; immunological‐related conditions or chronic inflammatory skin diseases; receiving blood thinning therapy or corticosteroids; required to take anti‐inflammatory drugs such as corticosteroids or ibuprofen more than twice a week Group 1 received oral EPA + DHA; group 2 received placebo
Prognostic factors	MMP‐8 (continuous data). Measurement method ELISA: MMP‐8, neutrophil collagenase, Biotrak ELISA kit; optical density against a purified MMP‐8 standard Human neutrophil elastase (data). Measurement method activity assay: InnoZyme Human Neutrophil Elastase Immunocapture Activity Assay Kit Time of measurement: baseline, 28 weeks and 56 weeks Wound fluid sampling method: occlusive dressings (Opsite (Smith & Nephew) 1‐1.5 hours)
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Selection bias	Unclear risk	Participants were those scheduled to begin receiving CVLU treatment. RCT population. Unclear whether this was representative.
Attrition bias	Unclear risk	Group 1: 5/21 participants missing (1 with health issues, 1 withdrew; 3 not analysed); group 2: 0/19 participants missing
Prognostic factor measurement	Unclear risk	Unclear if active protease measured
Outcome measurement	High risk	Ulcer size stated to be measured by principal investigator
Adjustment factors	High risk	Inadequate: none of the key confounders taken into account in the design or analysis
Analysis and reporting	High risk	Analysis as correlation used protease measurements at 4 weeks and 8 weeks only (even though measured at baseline). Results not given separately for intervention groups, even though intervention was designed to address protease levels
Overall risk of bias	High risk