Correa 2000.

Methods	RCT
Participants	Country: Colombia, two communities in Narino Province. 976 participants with confirmed histologic diagnoses of multifocal non‐metaplastic atrophy and/or intestinal metaplasia, 2 precancerous lesions. Mean age 51.1 years (range 29‐69 years), 46.1% male. Method to confirm presence of H. pylori: histological examination of gastric biopsies obtained at upper GI endoscopy. Only 852 out of 976 participants were eligible and treated. Study period: started in 1991
Interventions	1. Bismuth subsalicylate 262 mg, amoxicillin 500 mg, and metronidazole 375 mg 3 times daily for 2 weeks, including regimens with or without dietary supplements (n = 437). 2. Placebo, including regimens with or without dietary supplements (n = 415). Participants assigned to anti‐H. pylori treatment who tested positive for H. pylori at 36 months were treated again for 14 days with amoxicillin (1 g twice a day), clarithromycin (500 mg twice a day), and either omeprazole (20 mg twice a day) or lansoprazole (30 mg twice a day). Factorial design: 8 different regimens: H. pylori eradication with or without one of the 4 dietary supplements of beta‐carotene (30 mg once per day) and/or ascorbic acid (1 g twice a day) or placebo: A) placebo only; B) anti‐H. pylori; C) beta‐carotene (BC); D) ascorbic acid (AA); E) H. pylori eradication + BC; F) H. pylori eradication + AA; G) BC + AA; and H) H. pylori eradication + BC + AA. Last point of follow‐up 6 years.
Outcomes	Histological examination of gastric biopsies obtained at upper GI endoscopy at 6 years. Primary outcome was "progression of preneoplastic lesions". Other outcomes: relative risks of progression, no change, and regression from multifocal non‐metaplastic atrophy and intestinal metaplasia.
Notes	1. High‐risk participants (all with confirmed histologic diagnoses of multifocal non‐metaplastic atrophy and/or intestinal metaplasia, 2 precancerous lesions), primary outcome was "progression of preneoplastic lesions". 2. Randomised to anti‐H. pylori triple therapy and/or dietary supplementation with AA, BC, or their corresponding placebos. 3. 976 were randomised, but only 852 were eligible and treated after randomisation (7 refused and 117 ineligible). 852 were included in the ITT analyses, and all randomised participants were included in the sensitivity analyses. 631 participants completed the trials and were included in the complete case analyses. 4. Details of gastric cancer data were reported in Correa 2001(a letter). 5. H. pylori eradication rate 58.0%
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated lists produced in New Orleans and applied in the field in Pasto, three strata: atrophy (without metaplasia), intestinal metaplasia, or dysplasia.
Allocation concealment (selection bias)	Low risk	Central randomisation, therefore allocation was concealed.
Blinding of participants and personnel (performance bias) All outcomes	High risk	No double‐blinding for eradication vs non‐eradication (because an appropriate placebo was not available for bismuth subsalicylate), double‐blinding only applied to supplements vs placebo: "After a factorial design, a double‐blind approach—i.e., study investigators and subjects were unaware of treatment assignments, supplements and placebos were provided in identical coded tablets by Hoffmann‐La Roche Inc"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	At the end of the study, a single experienced pathologist, blinded to treatment assignment and all other study variables, examined all biopsy specimens collected at baseline and after 72 months of follow‐up.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	976 were randomised but only 852 were eligible and treated after randomisation (7 refused and 117 ineligible). 852 were included in the ITT analyses, and all randomised participants were included in the sensitivity analyses. 631 participants completed the trial and were included in the complete case analysis. 221 participants withdrew before their 72‐month evaluation: 102 quit treatment, 59 were lost to follow‐up, 34 dropped out of the study because of pregnancy and other medical conditions, 18 died of causes unrelated to gastric cancer, and 8 developed cancer other than gastric cancer. The average rate of loss was 4.3% per year over the 6‐year trial. Withdrew in 72 months = 117 (26.8%) vs 104 (25%) in all H. pylori eradication arms vs control arms. However, it is likely those who had cancer would have come back for treatment although these individuals did not complete the follow‐up.
Selective reporting (reporting bias)	Unclear risk	No data were reported for deaths from gastric cancer or adverse events.
Other bias	Low risk	No other risk of bias is noted.