Guldager 1992.

Study characteristics
Methods	Study design: randomised, double‐blind trial Intention‐to‐treat: not stated Country: Denmark Setting: outpatient clinic
Participants	Number randomised: N = 159 (EDTA n = 80; placebo n = 79) Exclusions post‐randomisation: N = 6 (EDTA n = 5; placebo n = 1) Losses to follow‐up: (more likely study withdrawal than dropout) N = 4 (2 deteriorations leading to vascular surgery, 1 death, 1 participant started chelation therapy at a private clinic) Age (mean years ± SD): EDTA 64 ± 7; placebo 66 ± 9 Gender (M n (%)): EDTA n = 48 (60%); placebo n = 55 (70%) Inclusion criteria: stable intermittent claudication for at least 12 months; pain‐free walking distance range of 50 m to 200 m, measured on treadmill at a speed of 3.6 km/hr with 10° inclination; ABPI of worse leg < 0.8 Exclusion criteria: vascular surgery within last 12 months, ischaemic rest pain or gangrene, moderate or severe venous insufficiency, renal insufficiency, diabetes mellitus, thyroid or parathyroid disorders, hepatic dysfunction, significant cardio‐pulmonary failure, e.g. acute myocardial infarction within last 12 months, tuberculosis, pregnancy, other conditions which could limit the person's walking distance or reliable interpretation of the study, people receiving anticoagulants, nitroglycerine or lithium, EDTA chelation therapy within last 24 months.
Interventions	Treatment: EDTA 3 g + NaCl 8.4 g in 1 litre normal saline solution x 20 infusions Control: 1 litre normal saline solution x 20 infusions Duration of treatment: 5 to 9 weeks Follow up: 3 and 6 months
Outcomes	Subjective evaluation Pain‐free and maximal walking distances ABPI (6 months duration of observation)
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was done in blocks of 10.
Allocation concealment (selection bias)	Unclear risk	Not explicitly stated.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	As this was a double‐blind study, blinding of participants and personnel was assured, at least until the end of the treatment period.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Outcome assessments done during the double‐blind study period had low risk of bias. As the code was broken after the last participant completed the treatment period, the 3‐month and 6‐month post‐treatment measurements were done with outcome assessors aware of treatment assignments and therefore had high risk of bias.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Six participants who did not complete treatment were not included in the subjective evaluation.
Selective reporting (reporting bias)	Low risk	All outcomes specified in the plan were reported.
Other bias	Low risk	Free from other sources of bias.