parallel randomized trial

NCT04847557

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Comparing the Efficacy and Safety of Tirzepatide Versus Placebo in Patients With Heart Failure With Preserved Ejection Fraction and Obesity (SUMMIT)

Heart failure with left ventricular ejection fraction above 40 percent NCT04847557S000047

Design

Randomized: 731
Start year: 2021
Treatment: 52 weeks, follow-up 156.54 weeks
Countries: Argentina, Brazil, China, India, Israel, Mexico, Russia, Taiwan, United States (129 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: age 40 or older; LVEF 50 percent or more; BMI 30 or more; NYHA II to IV; KCCQ-CSS 80 or less

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: yes
Primary estimand: treatment policy
Analysis population: randomized
Missing data: multiple imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	tirzepatide Tirzepatide MTD up to 15 mg	usual heart failure therapy; lifestyle: not reported	364	364
A2	Placebo Placebo	usual heart failure therapy; lifestyle: not reported	367	367

Baseline characteristics

As printed in the trial reports or registry, per arm or for the whole trial.

Characteristic	Statistic	Tirzepatide MTD up to 15 mg A1	Placebo A2
age	mean (years)	65.5	65.0
age	sd (years)	10.5	10.9
asian	n	58	73
asian	percent	15.9	19.9
black	n	22	14
black	percent	6.0	3.8
bmi	mean (kg/m2)	38.3	38.2
bmi	sd (kg/m2)	6.4	7.0
egfr	mean (mL/min/1.73 m2)	55.5	55.1
egfr	sd (mL/min/1.73 m2)	23.1	21.7
female	n	200	193
female	percent	54.9	52.6
hispanic	n	195	205
hispanic	percent	53.6	55.9
lvef	mean (percent)	61.0	60.6
lvef	sd (percent)	6.5	6.2
other race american indian alaska native pacific islander	n	26	24
other race american indian alaska native pacific islander	percent	7.1	6.5
other race american indian alaska native	n	24	23
other race multiple	n	2	0
other race multiple	percent	0.5	0.0
other race native hawaiian pacific islander	n	2	1
sbp	mean (mmHg)	127.9	128.2
sbp	sd (mmHg)	13.1	13.7
sglt2i use	n	69	57
sglt2i use	percent	19.0	15.5
uacr	median (g/kg)	17	20
uacr	q1 (g/kg)	8	8
uacr	q3 (g/kg)	47	65
waist	mean (cm)	120	120
waist	sd (cm)	15	14
weight	mean (kg)	102.9	103.1
weight	sd (kg)	21.7	22.7
white	n	256	256
white	percent	70.3	69.8

Results

65 adjudicated result lines, grouped by outcome. Open an outcome to see its values.

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				5 / 364	not stated; safety; registry:adverse_events
	A2	events				3 / 367	not stated; safety; registry:adverse_events

All cause mortality (3 lines; O20)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			19 / 364	not stated; modified itt; registry:outcomes
A1 vs A2	hr	1.245	0.633 to 2.452		not stated; modified itt; registry:outcomes
A2	events			15 / 367	not stated; modified itt; registry:outcomes

Hospitalization for heart failure (10 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	3 / 364	not stated; safety; cardiac failure congestive; registry:adverse_events
A1	events	1 / 364	not stated; safety; cardiac failure acute; registry:adverse_events
A1	events	1 / 364	not stated; safety; cardiac failure chronic; registry:adverse_events
A1	events	12 / 364	not stated; safety; cardiac failure; registry:adverse_events
A1	events	0 / 364	not stated; safety; heart failure with preserved ejection fraction; registry:adverse_events
A2	events	1 / 367	not stated; safety; cardiac failure acute; registry:adverse_events
A2	events	1 / 367	not stated; safety; cardiac failure chronic; registry:adverse_events
A2	events	12 / 367	not stated; safety; cardiac failure congestive; registry:adverse_events
A2	events	18 / 367	not stated; safety; cardiac failure; registry:adverse_events
A2	events	1 / 367	not stated; safety; heart failure with preserved ejection fraction; registry:adverse_events

Heart failure events (4 lines; O23B)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1 vs A2	hr	0.539	0.342 to 0.850		not stated; modified itt; registry:outcomes
A1	events			29 / 364	not stated; modified itt; registry:outcomes
A1 vs A2	hr	0.41	0.22 to 0.75		treatment policy; randomized; R0018803:Results
A2	events			52 / 367	not stated; modified itt; registry:outcomes

Health related quality of life total score (any instrument) (3 lines; O24C)

Week	Arm	Statistic	Estimate	95% CI	Detail
52	A1	change	0.12 points	0.10 to 0.14	treatment policy; randomized; R0018803:Results
52	A1 vs A2	md	0.06 points	0.03 to 0.09	treatment policy; randomized; R0018803:Results
52	A2	change	0.06 points	0.04 to 0.08	treatment policy; randomized; R0018803:Results

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				96 / 364	not stated; safety; registry:adverse_events
	A2	events				94 / 367	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 364	not stated; randomized; registry:flow
	A2	events				0 / 367	not stated; randomized; registry:flow

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	62 / 364	not stated; safety; registry:adverse_events
A1	events	1 / 364	not stated; safety; registry:adverse_events
A2	events	23 / 367	not stated; safety; registry:adverse_events
A2	events	1 / 367	not stated; safety; registry:adverse_events

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	38 / 364	not stated; safety; registry:adverse_events
A1	events	1 / 364	not stated; safety; registry:adverse_events
A2	events	7 / 367	not stated; safety; registry:adverse_events
A2	events	1 / 367	not stated; safety; registry:adverse_events

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	65 / 364	not stated; safety; registry:adverse_events
A1	events	2 / 364	not stated; safety; registry:adverse_events
A2	events	23 / 367	not stated; safety; registry:adverse_events
A2	events	0 / 367	not stated; safety; registry:adverse_events

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				54 / 364	not stated; safety; registry:adverse_events
	A2	events				22 / 367	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (8 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 364	not stated; safety; cholecystitis chronic; registry:adverse_events
A1	events	6 / 364	not stated; safety; cholecystitis acute; registry:adverse_events
A1	events	1 / 364	not stated; safety; cholecystitis; registry:adverse_events
A1	events	1 / 364	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	0 / 367	not stated; safety; cholecystitis chronic; registry:adverse_events
A2	events	0 / 367	not stated; safety; cholecystitis; registry:adverse_events
A2	events	1 / 367	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	4 / 367	not stated; safety; cholecystitis acute; registry:adverse_events

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	2 / 364	not stated; safety; obstructive pancreatitis; registry:adverse_events
A1	events	1 / 364	not stated; safety; registry:adverse_events
A2	events	0 / 367	not stated; safety; obstructive pancreatitis; registry:adverse_events
A2	events	0 / 367	not stated; safety; registry:adverse_events

Gastroparesis (2 lines; O37A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 364	not stated; safety; diabetic gastroparesis; registry:adverse_events
	A2	events				0 / 367	not stated; safety; diabetic gastroparesis; registry:adverse_events

Intestinal obstruction or ileus (2 lines; O37B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 364	not stated; safety; registry:adverse_events
	A2	events				0 / 367	not stated; safety; registry:adverse_events

Cardiovascular death or heart failure events (5 lines; O40)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1 vs A2	hr	0.67	0.45 to 0.99		treatment policy; randomized; R0018803:Figure 1A
A1 vs A2	hr	0.67	0.46 to 0.99		treatment policy; randomized; R0018803:Results
A1	events			36 / 364	not stated; modified itt; registry:outcomes
A1 vs A2	hr	0.62	0.41 to 0.95		treatment policy; randomized; R0018803:Results
A2	events			56 / 367	not stated; modified itt; registry:outcomes

KCCQ clinical summary score change (4 lines; O41)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1 vs A2	md	9.8 points		7.1 to 12.5		while on treatment; randomized; R0018803:Results
52	A1	change	19.51 points	1.24		301	not stated; modified itt; registry:outcomes
52	A1 vs A2	md	6.9 points		3.3 to 10.6		treatment policy; randomized; R0018803:Results
52	A2	change	12.68 points	1.25		313	not stated; modified itt; registry:outcomes