parallel randomized trial

STEP-HFpEF

Effect of Semaglutide 2.4 mg Once Weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction

Overweight or obesity without diabetes (adults)Heart failure with left ventricular ejection fraction above 40 percent NCT04788511S002012

Design

Randomized: 529
Start year: 2021
Treatment: 52 weeks, follow-up 57 weeks
Countries
Sponsor: Novo Nordisk A/S (industry)
Eligibility: LVEF 45 percent or more; NYHA II to IV; BMI 30 or more; KCCQ-CSS below 90; no diabetes, HbA1c below 6.5 percent

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: not reported
Primary estimand: treatment policy
Analysis population: full analysis
Missing data: multiple imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 2.4 mg subcutaneous once weekly Semaglutide 2.4 mg	standard of care for heart failure; lifestyle: standard	263	263
A2	Placebo Placebo	standard of care for heart failure; lifestyle: standard	266	266

Baseline characteristics

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

Characteristic	Statistic	Semaglutide 2.4 mg subcutaneous once weekly A1	Placebo A2	Whole trial ALL
age	mean (years)	69	68
age	sd (years)	9	10
asian	n	0	0
black	n	8	13
bmi: 30 to less than 35	n			180
bmi: 30 to less than 35	percent			34.0
bmi: 35 to less than 40	n			171
bmi: 35 to less than 40	percent			32.3
bmi: 40 or more	n			178
bmi: 40 or more	percent			33.7
bmi	median (kg/m2)			37.0
bmi	q1 (kg/m2)			33.7
bmi	q3 (kg/m2)			41.4
established cvd: coronary artery disease	n			98
established cvd: coronary artery disease	percent			18.5
female	n	149	148
hispanic	n	15	21
lvef: 45 to less than 50	n			85
lvef: 45 to less than 50	percent			16.1
lvef: 50 to less than 60	n			215
lvef: 50 to less than 60	percent			40.6
lvef: 60 or more	n			229
lvef: 60 or more	percent			43.3
lvef	median (percent)			57.0
lvef	q1 (percent)			50.0
lvef	q3 (percent)			60.0
other race american indian alaska native	n	0	0
other race multiple	n	0	0
other race native hawaiian pacific islander	n	0	0
sbp	median (mmHg)			133
sbp	q1 (mmHg)			121.0
sbp	q3 (mmHg)			144.0
waist	median (cm)			119.4
waist	q1 (cm)			110.5
waist	q3 (cm)			128.0
weight	median (kg)			105.1
weight	q1 (kg)			92.4
weight	q3 (kg)			120.8
white	n	255	252

Results

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

Systolic blood pressure change (2 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-6.4 mmHg	19.0		246	treatment policy; full analysis; registry:outcomes
52	A2	change	-1.1 mmHg	17.5		243	treatment policy; full analysis; registry:outcomes

Percent body weight change (3 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	percent change	-13.9 percent	8.1		246	treatment policy; full analysis; registry:outcomes
52	A1 vs A2	md	-10.7 percent		-11.9 to -9.4		treatment policy; full analysis; registry:outcomes
52	A2	percent change	-2.5 percent	5.6		242	treatment policy; full analysis; registry:outcomes

Weight loss of 10 percent or more (2 lines; O11B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	responders	65.9			246	treatment policy; full analysis; registry:outcomes
52	A2	responders	9.5			242	treatment policy; full analysis; registry:outcomes

Weight loss of 15 percent or more (2 lines; O11C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	responders	43.9			246	treatment policy; full analysis; registry:outcomes
52	A2	responders	2.1			242	treatment policy; full analysis; registry:outcomes

Weight loss of 20 percent or more (2 lines; O11D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	responders	23.6			246	treatment policy; full analysis; registry:outcomes
52	A2	responders	0.4			242	treatment policy; full analysis; registry:outcomes

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				5 / 263	not stated; safety; registry:adverse_events
	A2	events				1 / 266	not stated; safety; registry:adverse_events

All cause mortality (8 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	2 / 89	not stated; randomized; bmi:30_to_less_than_35; R0020464:Results
A1	events	3 / 263	not stated; safety; registry:adverse_events
A1	events	0 / 88	not stated; randomized; bmi:35_to_less_than_40; R0020464:Results
A1	events	1 / 86	not stated; randomized; bmi:40_or_more; R0020464:Results
A2	events	2 / 83	not stated; randomized; bmi:35_to_less_than_40; R0020464:Results
A2	events	0 / 91	not stated; randomized; bmi:30_to_less_than_35; R0020464:Results
A2	events	2 / 92	not stated; randomized; bmi:40_or_more; R0020464:Results
A2	events	4 / 266	not stated; safety; registry:adverse_events

Hospitalization for heart failure (8 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	1 / 263	not stated; safety; left ventricular failure; registry:adverse_events
A1	events	1 / 263	not stated; safety; cardiac failure acute; registry:adverse_events
A1	events	0 / 263	not stated; safety; cardiac failure congestive; registry:adverse_events
A1	events	0 / 263	not stated; safety; cardiac failure; registry:adverse_events
A2	events	0 / 266	not stated; safety; cardiac failure acute; registry:adverse_events
A2	events	3 / 266	not stated; safety; cardiac failure congestive; registry:adverse_events
A2	events	12 / 266	not stated; safety; cardiac failure; registry:adverse_events
A2	events	0 / 266	not stated; safety; left ventricular failure; registry:adverse_events

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	16.8 points	18.3		243	treatment policy; full analysis; registry:outcomes
52	A1 vs A2	md	7.5 points		4.4 to 10.6		treatment policy; full analysis; R0020409:Results
52	A2	change	10.9 points	17.5		237	treatment policy; full analysis; registry:outcomes

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				35 / 263	not stated; safety; registry:adverse_events
	A2	events				71 / 266	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				0 / 263	not stated; randomized; registry:flow
	A2	events				0 / 266	not stated; randomized; registry:flow

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				45 / 263	not stated; safety; registry:adverse_events
	A2	events				7 / 266	not stated; safety; registry:adverse_events

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	17 / 263	not stated; safety; registry:adverse_events
A1	events	1 / 263	not stated; safety; registry:adverse_events
A2	events	3 / 266	not stated; safety; registry:adverse_events
A2	events	1 / 266	not stated; safety; registry:adverse_events

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	24 / 263	not stated; safety; registry:adverse_events
A1	events	3 / 263	not stated; safety; registry:adverse_events
A2	events	10 / 266	not stated; safety; registry:adverse_events
A2	events	0 / 266	not stated; safety; registry:adverse_events

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				17 / 263	not stated; safety; registry:adverse_events
	A2	events				7 / 266	not stated; safety; registry:adverse_events

Discontinuation due to gastrointestinal adverse events (2 lines; O27E)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 263	not stated; randomized; registry:flow
	A2	events				0 / 266	not stated; randomized; registry:flow

Gallbladder and biliary disease (6 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 263	not stated; safety; bile duct stone; registry:adverse_events
A1	events	2 / 263	not stated; safety; cholelithiasis; registry:adverse_events
A1	events	1 / 263	not stated; safety; cholecystitis; registry:adverse_events
A2	events	2 / 266	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	0 / 266	not stated; safety; bile duct stone; registry:adverse_events
A2	events	0 / 266	not stated; safety; cholecystitis; registry:adverse_events

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 263	not stated; safety; obstructive pancreatitis; registry:adverse_events
	A2	events				1 / 266	not stated; safety; obstructive pancreatitis; 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 / 263	not stated; safety; small intestinal obstruction; registry:adverse_events
	A2	events				1 / 266	not stated; safety; small intestinal obstruction; registry:adverse_events

KCCQ clinical summary score change (3 lines; O41)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	16.8 points	17.9		243	treatment policy; full analysis; registry:outcomes
52	A1 vs A2	md	7.8 points		4.8 to 10.9		treatment policy; full analysis; R0020409:Results
52	A2	change	10.3 points	17.3		237	treatment policy; full analysis; registry:outcomes