Dataset Information

Quality of life, patient satisfaction, and cardiovascular outcomes of the randomised 2 x 3 factorial Copenhagen insulin and Metformin therapy (CIMT) trial - A detailed statistical analysis plan.

ABSTRACT:

Background

The evidence on the effects of metformin and insulin in type 2 diabetes patients on quality of life, patient satisfaction, and cardiovascular outcomes is unclear.

Methods

The Copenhagen Insulin and Metformin Therapy (CIMT) trial is an investigator-initiated multicentre, randomised, placebo-controlled trial with a 2 × 3 factorial design conducted at eight hospitals in Denmark. Participants with type 2 diabetes were randomised to metformin (n = 206) versus placebo (n = 206); in combination with open-label biphasic insulin aspart one to three times daily (n = 137) versus insulin aspart three times daily in combination with insulin detemir once daily (n = 138) versus insulin detemir once daily (n = 137).We present a detailed description of the methodology and statistical analysis of the clinical CIMT outcomes including a detailed description of tests of the assumptions behind the statistical analyses. The outcomes are quality of life (Short Form Health Survey (SF-36)), Diabetes Medication Satisfaction Questionnaire, and Insulin Treatment Satisfaction Questionnaire (assessed at entry and 18 months after randomisation) and cardiovascular outcomes including time to a composite of either myocardial infarction, stroke, peripheral amputation, coronary revascularisation, peripheral revascularisation, or death.

Discussions

This statistical analysis plan ensure the highest possible quality of the subsequent post-hoc analyses.

Trial registration

The protocol was approved by the Regional Committee on Biomedical Research Ethics (H-D-2007-112), the Danish Medicines Agency (EudraCT: 2007-006665-33 CIMT), and registered within ClinicalTrials.gov (NCT00657943, 8^th of April 2008).

SUBMITTER: Olsen MH

PROVIDER: S-EPMC10009439 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Quality of life, patient satisfaction, and cardiovascular outcomes of the randomised 2 x 3 factorial Copenhagen insulin and Metformin therapy (CIMT) trial - A detailed statistical analysis plan.

Olsen Markus Harboe MH Almdal Thomas P TP Madsbad Sten S Ovesen Christian C Gluud Christian C Sneppen Simone B SB Breum Leif L Hedetoft Christoffer C Krarup Thure T Lundby-Christensen Louise L Mathiesen Elisabeth R ER Røder Michael E ME Vestergaard Henrik H Wiinberg Niels N Jakobsen Janus C JC

Contemporary clinical trials communications 20230224

<h4>Background</h4>The evidence on the effects of metformin and insulin in type 2 diabetes patients on quality of life, patient satisfaction, and cardiovascular outcomes is unclear.<h4>Methods</h4>The Copenhagen Insulin and Metformin Therapy (CIMT) trial is an investigator-initiated multicentre, randomised, placebo-controlled trial with a 2 × 3 factorial design conducted at eight hospitals in Denmark. Participants with type 2 diabetes were randomised to metformin (n = 206) versus placebo (n = 20 ...[more]

PMID: 36923108

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Project description:ObjectiveTo assess the effect of metformin versus placebo both in combination with insulin analogue treatment on changes in carotid intima-media thickness (IMT) in patients with type 2 diabetes.Design and settingInvestigator-initiated, randomised, placebo-controlled trial with a 2 × 3 factorial design conducted at eight hospitals in Denmark.Participants and interventions412 participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥ 7.5% (≥ 58 mmol/mol); body mass index >25 kg/m2) were in addition to open-labelled insulin treatment randomly assigned 1:1 to 18 months blinded metformin (1 g twice daily) versus placebo, aiming at an HbA1c ≤ 7.0% (≤ 53 mmol/mol).OutcomesThe primary outcome was change in the mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight and hypoglycaemic and serious adverse events were other prespecified outcomes.ResultsChange in the mean carotid IMT did not differ significantly between the groups (between-group difference 0.012 mm (95% CI -0.003 to 0.026), p=0.11). HbA1c was more reduced in the metformin group (between-group difference -0.42% (95% CI -0.62% to -0.23%), p<0.001)), despite the significantly lower insulin dose at end of trial in the metformin group (1.04 IU/kg (95% CI 0.94 to 1.15)) compared with placebo (1.36 IU/kg (95% CI 1.23 to 1.51), p<0.001). The metformin group gained less weight (between-group difference -2.6 kg (95% CI -3.3 to -1.8), p<0.001). The groups did not differ with regard to number of patients with severe or non-severe hypoglycaemic or other serious adverse events, but the metformin group had more non-severe hypoglycaemic episodes (4347 vs 3161, p<0.001).ConclusionsMetformin in combination with insulin did not reduce carotid IMT despite larger reduction in HbA1c, less weight gain, and smaller insulin dose compared with placebo plus insulin. However, the trial only reached 46% of the planned sample size and lack of power may therefore have affected our results.Trial registration numberNCT00657943; Results.

Project description:ObjectiveTo assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes.Design and settingInvestigator-initiated, randomised, placebo-controlled trial with a 2 × 3 factorial design, conducted at 8 hospitals in Denmark.Participants and interventionsParticipants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥ 7.5% (≥ 58 mmol/mol), body mass index >25 kg/m(2)) were, in addition to metformin versus placebo, randomised to 18 months open-label biphasic insulin aspart 1-3 times daily (n=137) versus insulin aspart 3 times daily in combination with insulin detemir once daily (n=138) versus insulin detemir alone once daily (n=137), aiming at HbA1c ≤ 7.0% (≤ 53 mmol/mol).OutcomesPrimary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight, and hypoglycaemic and serious adverse events were other prespecified outcomes.ResultsCarotid IMT change did not differ between groups (biphasic -0.009 mm (95% CI -0.022 to 0.004), aspart+detemir 0.000 mm (95% CI -0.013 to 0.013), detemir -0.012 mm (95% CI -0.025 to 0.000)). HbA1c was more reduced with biphasic (-1.0% (95% CI -1.2 to -0.8)) compared with the aspart+detemir (-0.4% (95% CI -0.6 to -0.3)) and detemir (-0.3% (95% CI -0.4 to -0.1)) groups (p<0.001). Weight gain was higher in the biphasic (3.3 kg (95% CI 2.7 to 4.0) and aspart+detemir (3.2 kg (95% CI 2.6 to 3.9)) compared with the detemir group (1.9 kg (95% CI 1.3 to 2.6)). Insulin dose was higher with detemir (1.6 IU/kg/day (95% CI 1.4 to 1.8)) compared with biphasic (1.0 IU/kg/day (95% CI 0.9 to 1.1)) and aspart+detemir (1.1 IU/kg/day (95% CI 1.0 to 1.3)) (p<0.001). Number of participants with severe hypoglycaemia and serious adverse events did not differ.ConclusionsCarotid IMT change did not differ between 3 insulin regimens despite differences in HbA1c, weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results.Trial registration numberNCT00657943.

Project description:IntroductionCoronary artery bypass grafting can be conducted using the radial artery as a bypass graft. However, it remains unclear which harvesting method is superior, i.e. endoscopic or open radial artery, and which site for proximal anastomosis of the radial artery has the greatest benefits?MethodsThe NEO Trial is a single site randomised clinical trial with a 2 × 2 factorial design. The first comparison assesses endoscopic versus open radial artery harvest with a primary outcome of hand function and secondary outcomes of neurological deficits through clinical exams and neurophysiological studies. The primary outcome is postoperatively hand function at three months. We anticipate a mean difference of 3 points with a standard deviation of 8 points, a power of 90%, and a type I error of 5%, resulting in a required sample size of 300 participants randomised 1:1. Secondary outcomes are neurological deficits (based on nerve conduction measurements, algometry test and von Frey hair test), clinical neurological examination of cutaneous sensibility, and registration of complications in the donor arm (haematoma formation, wound dehiscence, and/or infection). The second comparison assesses two different proximal anastomotic sites, i.e. aorto-radial anastomosis versus mammario-radial anastomosis. The primary outcome is a composite of cerebrovascular events and the secondary outcome is graft patency evaluation by multi-slice computer tomography-scan. These outcomes will be assessed at 1 year postoperatively, and the results of this comparison will be exploratory only. Both comparisons will be analysed using intention-to-treat and intervention groups will be compared using linear regression, logistic regression, or Mann-Whitney U test depending on data type. Two independent statisticians will follow the present plan and conduct the analyses which will hereafter be fused into a final analysis based on consensus.ConclusionThis detailed analysis plan will increase the validity of the NEO trial results by predefining the statistical analysis in detail.Trial registrationClinicalTrials.gov identifier: NCT01848886 . Registered 25 February 2013. Danish Ethics committee number: H-3-2012-116. Danish Data Protection Agency: 2007-58-0015/jr. n:30-0838.

Dataset Information

Quality of life, patient satisfaction, and cardiovascular outcomes of the randomised 2 x 3 factorial Copenhagen insulin and Metformin therapy (CIMT) trial - A detailed statistical analysis plan.

Background

Methods

Discussions

Trial registration

Publications

Quality of life, patient satisfaction, and cardiovascular outcomes of the randomised 2 x 3 factorial Copenhagen insulin and Metformin therapy (CIMT) trial - A detailed statistical analysis plan.

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