Trial Outcomes & Findings for Metformin in Insulin Resistant Left Ventricular (LV) Dysfunction (TAYSIDE Trial) (NCT NCT00473876)

Results Overview

Peak VO2 after 4 months of intervention with either metformin or placebo. The Mean difference between baseline and after 4 months was analyzed using t-test comparing metformin and placebo.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

62 participants

Primary outcome timeframe

4 months

Results posted on

2013-06-06

Participant Flow

Patients with symptomatic CHF were recruited from out patient cardiology clinics and local echocardiography database. Eligible patients were approached to have a fasting blood test to determine their fasting insulin resistance index (FIRI). CHF patients with a FIRI \>2.7 were considered to have IR and invited to participate in the study.

127 patients were invited for screening.53 patients were excluded based on exclusion criteria.12 patients decided not to continue with the study after screening.62 patients were randomised using a computer generated sequence.Metformin was started at lower dose of 500mg bd for 2 weeks. Doses were up titrated if well tolerated to the target dose.

Participant milestones

Participant milestones
Measure	Metformin Receiving Metformin for 4 months with a target dose of 1000mg twice a day	Placebo Matched Placebo for 4 months
Overall Study STARTED	39	23
Overall Study COMPLETED	36	22
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Metformin Receiving Metformin for 4 months with a target dose of 1000mg twice a day	Placebo Matched Placebo for 4 months
Overall Study Lost to Follow-up	3	1

Baseline Characteristics

Metformin in Insulin Resistant Left Ventricular (LV) Dysfunction (TAYSIDE Trial)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metformin n=39 Participants Receiving Metformin for 4 months with a target dose of 1000mg twice a day	Placebo n=23 Participants Matched Placebo for 4 months	Total n=62 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	23 Participants n=93 Participants	9 Participants n=4 Participants	32 Participants n=27 Participants
Age, Categorical >=65 years	16 Participants n=93 Participants	14 Participants n=4 Participants	30 Participants n=27 Participants
Age Continuous	64 years STANDARD_DEVIATION 8 • n=93 Participants	68 years STANDARD_DEVIATION 7 • n=4 Participants	65 years STANDARD_DEVIATION 8 • n=27 Participants
Sex: Female, Male Female	4 Participants n=93 Participants	1 Participants n=4 Participants	5 Participants n=27 Participants
Sex: Female, Male Male	35 Participants n=93 Participants	22 Participants n=4 Participants	57 Participants n=27 Participants
Region of Enrollment United Kingdom	39 participants n=93 Participants	23 participants n=4 Participants	62 participants n=27 Participants

PRIMARY outcome

Timeframe: 4 months

Population: .In the metformin group,3 patients were lost to follow up therefore excluded from analysis.5 patients were discontinued on medications due to side effects, however,were included in our intention to treat analysis.In the placebo group,1 patient was lost to follow up and was excluded from analysis

Peak VO2 after 4 months of intervention with either metformin or placebo. The Mean difference between baseline and after 4 months was analyzed using t-test comparing metformin and placebo.

Outcome measures

Outcome measures
Measure	Metformin Arm n=36 Participants Peak VO2 mean difference between baseline and after 4 months of metformin was analysed	Placebo n=22 Participants Peak VO2 mean difference between baseline and after 4 months of placebo
Peak VO2	-0.38 ml/kg/min Standard Deviation 1.4	3.6 ml/kg/min Standard Deviation 3.9

SECONDARY outcome

Timeframe: 4 months

Population: 39 patients were randomized with 3 dropped out. Therefore, 36 were included in the analysis. There was 1 patient who dropped out in the placebo arm and hence 22 patients were analysed.

VE/VCO2 Slope, measurement of the abnormal ventilatory response to exercise identified by an increased slope of ventilation (L/min) vs. CO2 production (VE/VCO2) (L/min) to incremental workload

Outcome measures

Outcome measures
Measure	Metformin Arm n=36 Participants Peak VO2 mean difference between baseline and after 4 months of metformin was analysed	Placebo n=22 Participants Peak VO2 mean difference between baseline and after 4 months of placebo
Possible Mechanisms That Can Explain the Improvement of Exercise Capacity	-4.45 Unitless Standard Deviation 10.72	-0.23 Unitless Standard Deviation 3.54

Adverse Events

Metformin

Serious events: 2 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Metformin n=39 participants at risk Receiving Metformin for 4 months with a target dose of 1000mg twice a day	Placebo n=23 participants at risk Matched Placebo for 4 months
Cardiac disorders Acute Coronary Syndrome	5.1% 2/39 • Number of events 2	0.00% 0/23
Renal and urinary disorders Prostate Cancer	0.00% 0/39	4.3% 1/23 • Number of events 1

Other adverse events

Other adverse events
Measure	Metformin n=39 participants at risk Receiving Metformin for 4 months with a target dose of 1000mg twice a day	Placebo n=23 participants at risk Matched Placebo for 4 months
Gastrointestinal disorders Diarrhoea	46.2% 18/39 • Number of events 18	13.0% 3/23 • Number of events 3

Additional Information

Professor Chim C Lang

University of Dundee

Phone: 0044(0)1382 496375

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place