Trial Outcomes & Findings for Metformin to Reduce Heart Failure After Myocardial Infarction (NCT NCT01217307)

Results Overview

The primary efficacy parameter of the GIPS-III trial is LVEF measured by cardiac MRI 4 months after randomization, based on an intention-to-treat analysis. It is hypothesized that metformin therapy will result in a higher ejection fraction after 4 months.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

380 participants

Primary outcome timeframe

4 months

Results posted on

2018-01-30

Participant Flow

Participant milestones

Participant milestones
Measure	Metformin metformin 500mg twice daily during 4 months Metformin: Metformin 500mg twice daily during 4 months	Placebo Placebo twice daily during 4 months Placebo: Placebo twice daily during 4 months
Overall Study STARTED	191	189
Overall Study COMPLETED	191	188
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Metformin metformin 500mg twice daily during 4 months Metformin: Metformin 500mg twice daily during 4 months	Placebo Placebo twice daily during 4 months Placebo: Placebo twice daily during 4 months
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Metformin to Reduce Heart Failure After Myocardial Infarction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metformin n=191 Participants metformin 500mg twice daily during 4 months Metformin: Metformin 500mg twice daily during 4 months	Placebo n=189 Participants Placebo twice daily during 4 months Placebo: Placebo twice daily during 4 months	Total n=380 Participants Total of all reporting groups
Age, Continuous	58.7 years STANDARD_DEVIATION 11.8 • n=5 Participants	58.8 years STANDARD_DEVIATION 11.5 • n=7 Participants	58.8 years STANDARD_DEVIATION 11.6 • n=5 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	48 Participants n=7 Participants	95 Participants n=5 Participants
Sex: Female, Male Male	144 Participants n=5 Participants	141 Participants n=7 Participants	285 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 months

Population: patients undergoing primary percutaneous coronary intervention (PCI) for STEMI

The primary efficacy parameter of the GIPS-III trial is LVEF measured by cardiac MRI 4 months after randomization, based on an intention-to-treat analysis. It is hypothesized that metformin therapy will result in a higher ejection fraction after 4 months.

Outcome measures

Outcome measures
Measure	Metformin n=191 Participants metformin 500mg twice daily during 4 months Metformin: Metformin 500mg twice daily during 4 months	Placebo n=189 Participants Placebo twice daily during 4 months Placebo: Placebo twice daily during 4 months
Improvement in Left Ventricular Ejection Fraction	53.1 % of LVEF Interval 51.6 to 54.6	54.8 % of LVEF Interval 53.5 to 56.1

SECONDARY outcome

Timeframe: 4 months and longterm follow-up

Cardiovascular events include major cardiac adverse events (MACE; death, recurrent MI, target lesion revascularization), stroke, non-elective hospitalizations for chest pain or heart failure, all recurrent coronary interventions, and internal cardiac defibrillator implantations. Mortality will be divided into cardiac and non-cardiac. Cardiac death will be divided into three categories: heart failure, sudden death and other. A cardiologist will confirm deaths from cardiovascular causes by examining medical records obtained from hospitals and attending physicians or from attending general practitioner if the patient died at home.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 months and longterm follow-up

markers of heart failure: neurohormones (e.g. NT-proBNP), renal function (e.g. MDRD); glycometabolic state: e.g. HbA1c.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 months after hospitalization

myocardial infarct size and transmural extent of infarction will be measured using Late Gadolinium Enhancement cardiac magnetic imaging

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 months

echocardiographic analysis of diastolic function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 months and long-term follow-up

measured by oral glucose tolerance testing and Glycated Hemoglobin according to current criteria

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 months

A per-protocol analysis, excluding patients diagnosed with new onset diabetes and treated with oral antihyperglycemic agents or insulin prior to cardiac MRI, will be performed as a secondary efficacy parameter

Outcome measures

Outcome data not reported

Adverse Events

Metformin

Serious events: 11 serious events

Other events: 73 other events

Deaths: 3 deaths

Placebo

Serious events: 6 serious events

Other events: 51 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Metformin n=191 participants at risk metformin 500mg twice daily during 4 months Metformin: Metformin 500mg twice daily during 4 months	Placebo n=188 participants at risk Placebo twice daily during 4 months Placebo: Placebo twice daily during 4 months
Cardiac disorders Reinfarction	4.2% 8/191 • Number of events 8	2.7% 5/188 • Number of events 5
Cardiac disorders Cardiovascular death	0.52% 1/191 • Number of events 1	0.00% 0/188
Cardiac disorders Target lesion revascularization	2.6% 5/191 • Number of events 5	2.1% 4/188 • Number of events 4

Other adverse events

Other adverse events
Measure	Metformin n=191 participants at risk metformin 500mg twice daily during 4 months Metformin: Metformin 500mg twice daily during 4 months	Placebo n=188 participants at risk Placebo twice daily during 4 months Placebo: Placebo twice daily during 4 months
Cardiac disorders Non-target lesion revascularization	20.9% 40/191 • Number of events 40	13.8% 26/188 • Number of events 26
Cardiac disorders CABG	5.2% 10/191 • Number of events 10	2.7% 5/188 • Number of events 5
Cardiac disorders Hospitalization for chest pain	12.0% 23/191 • Number of events 23	10.6% 20/188 • Number of events 20

Additional Information

Dr. I.C.C. van der Horst

University Medical Center Groningen

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place