Andreeva 2011.
| Methods | Multicentre, randomised, placebo‐controlled, 2 x 2 factorial trial An ancillary study of SU.FOL.OM3 |
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| Participants | Main study took place from 2003‐2009. Quote: "As part of the SU.FOL.OM3 assessment battery, the F‐TICS‐m was administered during 2007‐2009 only to participants who had completed 4 years of follow‐up." Location: 257 participating centres in France Recruitment: recruitment of subjects done through a network of 417 cardiologists and neurologists from all over France, working either in general hospitals, independently or in rehabilitation centres. Treatment with tablets at home. Sample size: 1881 participants were eligible for the cognitive study (had completed 4 years of follow‐up in main study); 1748 completed the cognitive assessment. · Number randomised in SU.FOL.OM3:
· Number completing cognitive study:
Group A (B Vitamins and Omega ‐3 PUFA) baseline characteristics:
Group B (Omega‐3 PUFA) baseline characteristics:
Group C (B vitamins) baseline characteristics:
Group D (Placebo) baseline characteristics:
Inclusion criteria: Men and women aged 45–80 y with a recent (1‐12 months prior to inclusion) myocardial infarction (MI), unstable angina, or ischaemic stroke were eligible for participation. There was no diagnostic criterion used to detect dementia/cognitive impairment. Instead, participants were given the Issac’s Set Test at baseline and results were stated as a Mean ± SD. Exclusion criteria: Patients incapable of understanding the study protocol or who refused to sign the informed consent, patients with a pathology that might interfere with homocysteine or omega‐3 fatty acid metabolism, in particular, those that use methotrexate for the treatment of a cancer or rheumatoid arthritis, chronic renal failure (plasma level of creatinine > 200 μmol/L or creatinine clearance < 40 mL/min), patients with a non‐cardiovascular pathology with a suspected survival time less than the 5 years period of the study (solid cancer, evolved dementia, leukaemia) and patients taking B vitamins or omega‐3 fatty acids. |
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| Interventions |
Intervention (n = 1748): Study supplements were given as 2 capsules administered orally once per day. The supplements were provided in a package containing 53 blisters of 7 × 2 capsules, each corresponding to one week of both treatments. A year’s supply was given at baseline and given again at each annual follow‐up appointment for 5 years in total. Group A (B vitamins and Omega‐3 PUFA): 5‐methyltetrahydrofolate (folate, 0.56 mg) and vitamins B6 (3 mg) and B12 (0.02 mg) and eicosapentaenoic and docosahexaenoic acids (600 mg) in a 2:1 ratio Group B (Omega‐3 PUFA): eicosapentaenoic and docosahexaenoic acids (600 mg) in a 2:1 ratio Group C (B Vitamins): 5‐methyltetrahydrofolate (folate, 0.56 mg) and vitamins B6 (3 mg) and B12 (0.02 mg) Group D (placebo): 2 placebo Capsules Comparator group (n = 425): 2 placebo tablets given once daily. The placebo capsules looked and tasted identical to the active supplements (taken from SU.FOL.OM3 trial paper). Use of additional interventions (common to all treatment arms): no |
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| Outcomes |
Outcomes of interest in the review: Global cognitive functioning: French version of the modified Telephone Interview for Cognitive Status (F‐TICS‐m) Episodic memory: delayed recall subdomain from F‐TICSm |
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| Notes |
Funding sources: The SU.FOL.OM3 trial was supported by the French Ministry of Research (grant R02010JJ), the Ministry of Health, Sodexo, Candia, Unilever, Danone, Roche Laboratories, Merck EPROVA AG, and Pierre Fabre Laboratories. Declarations of interest: none declared Treatment adherence: Compliance with treatment was self‐reported in the biannual questionnaires (or by telephone interview). Compliance was defined as taking at least 80% of the allocated treatment. (taken from SU.FOL.OM3 trial paper). |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "We used computerized block randomisation (block size = 8) with stratification by sex, age (45–54, 55–64, and 65–80 y), prior CVD, and city of residence.” Comment: adequate method of random sequence generation. |
| Allocation concealment (selection bias) | Low risk | Comment: no information. Centralised, computerised system, likely to be adequately concealed |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: “The placebo capsules looked and tasted identical to the active supplements" Comment: probably blinded |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: did not mention blinding of study personnel including outcome assessors |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: 24.8% of participants in SU.FOL.OM3 were lost to follow‐up over the first 4 years and before the onset of the cognitive study. These participants appeared to be well balanced between groups. 133/1881 (7%) participants eligible for the cognitive study were excluded: 72 (3.8%) were unable to complete the cognitive assessment and 61 refused to participate. Treatment allocations of these participants were not reported. Cognitive data were reported for 69.9% of the randomised participants. |
| Selective reporting (reporting bias) | Unclear risk | Quote: “No changes to the outcomes of interest were made after launching the trial" Comment: The authors have stated no changes to the outcomes were made, however, these were not previously published in a protocol as this is an ancillary study and the main study protocol did not mention any cognitive outcomes. |
| Other bias | Low risk | No other risks identified |