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. 2023 Feb 24:33:101095.
doi: 10.1016/j.conctc.2023.101095. eCollection 2023 Jun.

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

Markus Harboe Olsen  1   2 , Thomas P Almdal  3 , Sten Madsbad  4 , Christian Ovesen  1   5 , Christian Gluud  1   6 , Simone B Sneppen  7 , Leif Breum  8 , Christoffer Hedetoft  8 , Thure Krarup  9 , Louise Lundby-Christensen  9 , Elisabeth R Mathiesen  3   10 , Michael E Røder  11 , Henrik Vestergaard  12   13 , Niels Wiinberg  14 , Janus C Jakobsen  1   6
Affiliations

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

Markus Harboe Olsen et al. Contemp Clin Trials Commun. .

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, 8th of April 2008).

Keywords: Clinical outcomes; Detailed statistical analysis plan; Insulin; Metformin; Quality of life; Randomised clinical trial; Type 2 diabetes.

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Conflict of interest statement

Sten Madsbad: Advisory boards: AstraZeneca; Boehringer Ingelheim; Eli Lilly; Intarcia Therapeutics; Merck Sharp & Dohme; Novartis; Novo Nordisk; Sanofi. Lecture fees: AstraZeneca; Boehringer Ingelheim; Merck Sharp & Dohme; Novo Nordisk; Sanofi. Research Grant Recipient: Novo Nordisk; Boehringer Ingelheim. Leif Breum: Advisory boards: AstraZeneca; Boehringer Ingelheim; Merck Sharp & Dohme; Novo Nordisk; Sanofi. Lecture fees: AstraZeneca; Lundbeck, Otsuka. Louise Lundby-Christensen, Christian Ovesen, Thomas Almdal: own shares in Novo Nordisk A/S. Elisabeth R Mathiesen: Advisory board: Novo Nordisk. Markus Harboe Olsen. Janus C Jakobsen, Christian Gluud, Simone B Sneppen, Christoffer Hedetoft, Michael E. Røder, Henrik Vestergaard, Niels Wiinberg, Thure Krarup: none declared.

Figures

Fig. 1
Fig. 1
– A study scheme of the factorial designed trial, where participants are ranodmised into both factors. Thus, each participant is allocated in both Factor 1 and Factor 2, and receives a combination of the two treatment schemes.
See this image and copyright information in PMC

References

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