Skip to main content
. 2017 Aug 17;2017(8):CD006612. doi: 10.1002/14651858.CD006612.pub5

B‐PROOF 2015.

Study characteristics
Methods Parallel design (2 arms
Multicentre study: yes (3 centres)
Country: The Netherlands
Follow‐up period (years): 2
Participants Randomised: 2919 (Original group of 'B‐vitamins for the PRevention Of Osteoporotic Fractures')

  1. Intervention: 1458

  2. Placebo: 1461


The following data belong to subgroup analysis on cardiovascular events (named as 'Vascular subgroup' by trial authors).
Randomised: 569

  1. Intervention: 274

  2. Placebo: 295


Age (Mean SD):

  1. Intervention: 72.5 (5.8)

  2. Placebo: 72.5 (5.3)


Gender (male %):

  1. Intervention: 55.9

  2. Placebo: 55.5


Homocysteine levels at baseline (median interquartile range ) (μmol/L):

  1. Intervention: 14.2 (13.0 to 16.3)

  2. Placebo: 14.3 (13.0 to 16.6)


Self‐reported cardiovascular medical history (intervention versus placebo):

  1. MI: 6.1% vs 10.2%

  2. Any type CVD: 21.0% vs 21.9%

  3. Cerebrovascular event: 7.5% vs 8.4%

  4. Hypercholesterolaemia: 25.1% vs 28.1%

  5. Diabetes: 10.8% vs 12.0%


Inclusion criteria:

  1. Age ≥ 65 years

  2. Plasma Hcy level between 12.0 μg/mol/L and 50.0 μg/mol/L


Exclusion criteria:

  1. Serum creatinine level >150 μg mol/L

  2. Cancer in the past 5 years (excluding non‐melanoma skin cancer),

  3. High doses of B‐vitamins use (intramuscular injections of vitamin B12 and/or folic acid intake > 300 μg/day)

  4. Permanent use of a wheel chair
Interventions

  1. Experimental: 400 μg folic acid and 500 μg vitamin B12

  2. Control: placebo

  3. Co‐intervention: 600 IU (15 μg) of vitamin D3 daily


Treatment duration: two years
Outcomes Outcomes related to vascular subgroup analysis:

  1. Any type of CVD: MI, angina pectoris, heart failure, cardiac valvular disease, or arrhythmia.

  2. Adverse events
Notes

  1. Identifier: Netherlands Trial Register NTR 1333 and NCT00696514

  2. Conducted between August 2008 and March 2011

  3. A priori sample estimation: yes

  4. Financial disclosures: Two authors declared to have received an unconditional grant of Merck and Co for vitamin D assessment in Longitudinal Aging Study Amsterdam and one of them received personal fees from Merck and Co and Bristol‐Myers Squibb.

  5. Other disclosures: none

  6. Funding/support: "supported and funded by The Netherlands Organization for Health Research and Development (ZonMw, Grant 6130.0031), the Hague; unrestricted grant from NZO (Dutch Dairy Association), Zoetermeer; Orthica, Almere; NCHA (Netherlands Consortium Healthy Ageing) Leiden/Rotterdam; Ministry of Economic Affairs, Agriculture, and Innovation (Project KB15‐004‐003), the Hague; Wageningen University, Wageningen; VU University Medical Center, Amsterdam; Erasmus Medical Center, Rotterdam." (Page 408).

  7. Rol of sponsor: "The sponsors do not have any role in the design or implementation of the study, data collection, data management, data analysis, data interpretation, or in the preparation, review, or approval of the manuscript" (Page 408).
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Quote "The random allocation sequence and randomization were generated and performed using SAS 9.2 by an independent research dietician." (Page 402)
Allocation concealment (selection bias) Low risk Quote "The random allocation sequence and randomization were generated and performed using SAS 9.2 by an independent research dietician." (Page 402)
Blinding of participants and personnel (performance bias)
All outcomes Low risk Quote "Intervention and placebo tablets were indistinguishable in taste, smell, and appearance. Both the participants and all researchers and research assistants were blinded to the study treatment" (Page 402)
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Insufficient information on blinding of outcome assessment to judge as 'high' or 'low' risk
Incomplete outcome data (attrition bias)
All outcomes High risk Follow‐up:
Experimental group: 94.8% (260/274)
Control: 80.3% (237/295)
Imbalance between comparison groups: 14.5%
Selective reporting (reporting bias) Low risk It is clear that the published reports relevant clinical outcomes
Other bias Low risk Other sources of bias not identified