Burrows 1986.

Methods	Parallel‐group, randomised controlled study; cross‐over design This multi‐centre study was conducted in Ireland and in the UK in a secondary setting at 3 different centres
Participants	23 participants with chronic eczema on palms or dorsa, with positive patch test to nickel Dropouts: 3 Inclusion criteria of the trial Chronic hand eczema and a positive patch test to 5% nickel sulphate Exclusion criteria of the trial Pregnancy Atopic eczema History of peptic ulcer, hepatic or renal disease Aberrations in serum iron, CPK, bilirubin, alkaline phosphatase, LDH, AST, ALT, creatinine, urea, urine analysis, and antinuclear factor Study population Gender: 21 female, 2 male Age: mean age 29.3 years, SD 13.3 years, range 19 to 66 years
Interventions	Intervention • Triethylenetetramine (Trientene) 300 mg daily for 6 weeks in an unknown number of participants Control intervention • Placebo for 6 weeks Cross‐over after 4‐week washout. The total expected duration of the study was thus 16 weeks; however the trial was terminated prematurely Duration 6 weeks
Outcomes	Primary outcomes of the trial Not defined Other outcomes Observer‐rated: improvement/no change/deterioration Participant‐rated: improvement/no change/deterioration Urinary nickel and copper excretion Adverse events
Notes	The trial was terminated due to a literature report on potential adverse events (teratogenicity). Study results were based on participants entered before termination. Results table is difficult to interpret in view of the cross‐over; probably based on 20 participants Declarations of interest: not stated Funding: not stated Sample size rationale: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "patients were allocated randomly" Comment: no further details on randomisation procedure
Allocation concealment (selection bias)	Unclear risk	No details about how allocation was concealed from participants and investigators
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "a multicentre, double‐blind, crossover trial was initiated to test the ability of...." Comment: participants and staff were probably blinded, as this is stated in the paper, and a placebo was used, but no details are given as to how this was achieved. It is not clear whether placebo was identical in appearance
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "a multicentre, double‐blind, crossover trial was initiated to test the ability of...." Comment: no details regarding observer blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No intention‐to‐treat analysis but per protocol (20 of 23 = more than 80%)
Selective reporting (reporting bias)	Unclear risk	No trial registration found. The outcome parameters used are very concise. The Materials and Methods section describes that observer‐ and participant‐rated scores would be used with regard to improvement/no change/deterioration; however, only one table shows improvement versus no improvement and worse, and it is unclear whether this was participant‐ or observer‐rated
Other bias	High risk	No baseline comparisons Diagnostic certainty: yes The study was ended prematurely