Chase.

Study characteristics
Methods	Study design: parallel‐group RCT Unit of randomization and analysis: individual Number randomized: Total: 16 Per group: 7 to captopril, 9 to placebo Sample size calculation: none reported
Participants	Country: USA Study period: not reported Type of diabetes: type 1 Participants’ status at baseline: Age,years, mean (SD): 22 (8.4) in the captopril group, 19.9 (4.4)  in the placebo group Gender, % women: 0% in captopril group and 4 (44%) in placebo group Race/ethnicity: not reported Duration of diabetes, years, mean (SD): 14.1 (3.5) Smokers, % current: not reported Blood pressure, mean (SD): SBP 118 (10.2) mmHg captopril, 113 (10.2) mmHg placebo DBP 78 (6.1) mmHg captopril, 78 (7.2) mmHg placebo Hypertension, %: 0% (all normotensive) Glycated hemoglobin, mean (SD): 8.8 (1.6) captopril; 8.0 (1.1) placebo BMI, mean (SD): not reported Severity of diabetic retinopathy: based on modified Airlie House system, 1 (no microaneurysm or other diabetic retinopathy lesion) to 6 (PDR) Captopril group: 0 with grade 1; 1 (14%) grade 2; 3 (43%) grade 3; 3 (43%) grade 4 Placebo group: 3 (33%) grade 1; 3 (33%) grade 2; 1 (11%) grade 3; 1 (11%) grade 4; 1 (11%) grade 6 Medical history: Myocardial infarction, %: not reported (unlikely at this age) Stroke, %: not reported (unlikely at this age) Equivalence of groups at baseline: retinopathy worse in captopril group; otherwise fair, given small sample size Inclusion criteria: insulin‐dependent type 1 diabetes, with an albumin excretion rate of 20 to 200 µg/min on 3 of 4 overnight urine collections Exclusion criteria: not otherwise reported
Interventions	Intervention 1: captopril 50 mg twice a day Intervention 2: placebo Length of follow‐up: Planned: 2 years Actual: 2 years
Outcomes	Primary outcome, as defined for this review: progression of DR by at least 1 step on the modified Airlie House classification based on 7‐field color photographs Secondary outcomes, as specified for this review: progression to PDR Other diabetic retinopathy outcomes: improvement of diabetic retinopathy by 1 or more grades Retinopathy diagnosis and monitoring: "Initially, all subjects underwent pupil dilation followed by direct ophthalmoscopy by two observers (a pediatrician and an ophthalmologist), slit‐lamp examination, color photography of the seven standard fields, and fluorescein angiography ... at six‐ to 12‐month intervals ... fluorescein angiograms were done only if verification of a change was necessary."  Grading of retinal changes was done using the modified Airlie House system" (Grades 1 to 6 [PDR]). "The final eye grade for the worst [sic] eye was determined by the ophthalmologist ... ." Participants (eyes) examined for the outcome: 16 Intervals at which outcomes were assessed: 6‐ to 12‐month intervals Cost of the interventions: not reported Quality of life: not reported Adverse outcomes: not reported Other outcomes reported from the study: albumin excretion rate, creatinine clearance rate, protein intake
Notes	Sources of funding: partial support from industry, foundation, and government Declaration of interest: not reported Class(es) of antihypertensive agents compared: ACEi Degree of blood pressure control achieved: no target blood pressure reported; 2‐year follow‐up blood pressure was similar to baseline blood pressure
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	“The subjects were randomized in a double‐blind study design.”
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Masking (performance bias and detection bias) Primary outcomes	Unclear risk	“double‐blind study design”
Masking (performance bias and detection bias) Secondary outcomes	High risk	Apparently the investigator assessed DR on photos and was also aware of treatment.
Incomplete outcome data (attrition bias) Primary outcome	Low risk	Data reported for all 16 participants.
Incomplete outcome data (attrition bias) Secondary outcomes	Low risk	Outcome reported for all participants.
Selective reporting (reporting bias)	Unclear risk	Unclear with available information
Other bias	Unclear risk	“Supported in part by Bristol‐Myers Squibb Company.” Too little information reported regarding methods to classify as low risk.