parallel randomized trial

ELIXA

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate Cardiovascular Outcomes During Treatment With Lixisenatide in Type 2 Diabetic Patients After an Acute Coronary Syndrome

Type 2 diabetes (adults)NCT01147250S001991

Design

Randomized: 6,068
Start year: 2010
Treatment: , follow-up 225.94 weeks
Countries: multinational
Sponsor: Sanofi (industry)
Eligibility: T2D with ACS within 180 days; age 30 or older; eGFR 30 or more; HbA1c 5.5 to 11.0 percent

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: yes
Primary estimand: not stated
Analysis population: randomized
Missing data

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Placebo Placebo	usual care per local guidelines; lifestyle: not reported	3,034	3,034
A2	Lixisenatide 20 ug subcutaneous once daily Lixisenatide 20 ug QD	usual care per local guidelines; lifestyle: not reported	3,034	3,034

Baseline characteristics

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

Characteristic	Statistic	Placebo A1	Lixisenatide 20 ug subcutaneous once daily A2	Whole trial ALL
age	mean (years)	60.6	59.9
age	sd (years)	9.6	9.7
asian	n	367	404
black	n	103	118
bmi	mean (kg/m2)	30.2	30.12
bmi	sd (kg/m2)	5.79	5.6
diabetes duration	mean (years)	9.38	9.2
diabetes duration	sd (years)	8.32	8.19
egfr	mean (mL/min/1.73 m2)			76
egfr	sd (mL/min/1.73 m2)			21
established cvd	percent			100
female	n	938	923
female	percent	30.9	30.4
hba1c	mean (percent)	7.64	7.72
hba1c	sd (percent)	1.28	1.32
hispanic	n	903	865
insulin use	n			2891
insulin use	percent			47.6
metformin use	n			4243
metformin use	percent			69.9
other agi use	n			181
other agi use	percent			3.0
other dpp4i use	n			226
other dpp4i use	percent			3.7
other race other	n	246	254
other sulfonylurea use	n			2266
other sulfonylurea use	percent			37.3
other tzd use	n			128
other tzd use	percent			2.1
sbp	mean (mmHg)			130
sbp	sd (mmHg)			17
uacr: 300 or more	n			389
uacr: 300 or more	percent			6.5
uacr: 30 to less than 300	n			1148
uacr: 30 to less than 300	percent			19.2
uacr: less than 30	n			4441
uacr: less than 30	percent			74.3
weight	mean (kg)	85.06	84.64
weight	sd (kg)	19.64	19.21
white	n	2318	2258

Results

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

Body weight change in kilograms (diabetes) (1 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
108.63	A2 vs A1	md	-0.7 kg				not stated; other; R0009517:Table 1

Level 2 or 3 hypoglycemia (participants) (6 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	554 / 3032	not stated; safety; registry:adverse_events
A1	events	10 / 3032	not stated; safety; registry:adverse_events
A1	events	3 / 3032	not stated; safety; registry:adverse_events
A2	events	5 / 3031	not stated; safety; registry:adverse_events
A2	events	609 / 3031	not stated; safety; registry:adverse_events
A2	events	2 / 3031	not stated; safety; registry:adverse_events

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				20 / 3032	not stated; safety; registry:adverse_events
	A2	events				20 / 3031	not stated; safety; registry:adverse_events

Four point MACE including unstable angina (7 lines; O21B)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			659 / 3034	not stated; randomized; registry:outcomes
A1	events			469 / 3034	not stated; randomized; registry:outcomes
A1	events			399 / 3034	not stated; randomized; registry:outcomes
A2	events			456 / 3034	not stated; randomized; registry:outcomes
A2	events			661 / 3034	not stated; randomized; registry:outcomes
A2	events			406 / 3034	not stated; randomized; registry:outcomes
A2 vs A1	hr	1.017	0.886 to 1.168		not stated; randomized; registry:outcomes

Hospitalization for heart failure (2 lines; O23)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				127 / 3034	not stated; randomized; R0009517:Table 1
	A2	events				122 / 3034	not stated; randomized; R0009517:Table 1

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				669 / 3032	not stated; safety; registry:adverse_events
	A2	events				625 / 3031	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 / 3034	not stated; randomized; registry:flow
	A2	events				0 / 3034	not stated; randomized; registry:flow

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	179 / 3032	not stated; safety; registry:adverse_events
A1	events	3 / 3032	not stated; safety; registry:adverse_events
A2	events	659 / 3031	not stated; safety; registry:adverse_events
A2	events	0 / 3031	not stated; safety; registry:adverse_events

Vomiting (6 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	82 / 3032	not stated; safety; registry:adverse_events
A1	events	0 / 3032	not stated; safety; registry:adverse_events
A1	events	0 / 3032	not stated; safety; faecal vomiting; registry:adverse_events
A2	events	257 / 3031	not stated; safety; registry:adverse_events
A2	events	2 / 3031	not stated; safety; registry:adverse_events
A2	events	1 / 3031	not stated; safety; faecal vomiting; registry:adverse_events

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	227 / 3032	not stated; safety; registry:adverse_events
A1	events	4 / 3032	not stated; safety; registry:adverse_events
A2	events	237 / 3031	not stated; safety; registry:adverse_events
A2	events	3 / 3031	not stated; safety; registry:adverse_events

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 3032	not stated; safety; registry:adverse_events
	A2	events				0 / 3031	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 / 3034	not stated; randomized; registry:flow
	A2	events				0 / 3034	not stated; randomized; registry:flow

Gallbladder and biliary disease (16 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 3032	not stated; safety; gallbladder abscess; registry:adverse_events
A1	events	1 / 3032	not stated; safety; bile duct stone; registry:adverse_events
A1	events	1 / 3032	not stated; safety; cholangitis; registry:adverse_events
A1	events	0 / 3032	not stated; safety; gallbladder polyp; registry:adverse_events
A1	events	7 / 3032	not stated; safety; cholecystitis acute; registry:adverse_events
A1	events	1 / 3032	not stated; safety; cholecystitis chronic; registry:adverse_events
A1	events	5 / 3032	not stated; safety; cholecystitis; registry:adverse_events
A1	events	6 / 3032	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	1 / 3031	not stated; safety; gallbladder polyp; registry:adverse_events
A2	events	1 / 3031	not stated; safety; bile duct stone; registry:adverse_events
A2	events	1 / 3031	not stated; safety; gallbladder abscess; registry:adverse_events
A2	events	10 / 3031	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	1 / 3031	not stated; safety; cholecystitis chronic; registry:adverse_events
A2	events	9 / 3031	not stated; safety; cholecystitis; registry:adverse_events
A2	events	0 / 3031	not stated; safety; cholangitis; registry:adverse_events
A2	events	13 / 3031	not stated; safety; cholelithiasis; registry:adverse_events

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	2 / 3032	not stated; safety; registry:adverse_events
A1	events	3 / 3032	not stated; safety; pancreatitis; registry:adverse_events
A2	events	0 / 3031	not stated; safety; registry:adverse_events
A2	events	2 / 3031	not stated; safety; pancreatitis; registry:adverse_events

Thyroid cancer (any) (2 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 3032	not stated; safety; papillary thyroid cancer; registry:adverse_events
	A2	events				1 / 3031	not stated; safety; papillary thyroid cancer; registry:adverse_events

Diabetic retinopathy complications (6 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	1 / 3032	not stated; safety; blindness unilateral; registry:adverse_events
A1	events	0 / 3032	not stated; safety; diabetic retinal oedema; registry:adverse_events
A1	events	3 / 3032	not stated; safety; vitreous haemorrhage; registry:adverse_events
A2	events	1 / 3031	not stated; safety; diabetic retinal oedema; registry:adverse_events
A2	events	0 / 3031	not stated; safety; blindness unilateral; registry:adverse_events
A2	events	1 / 3031	not stated; safety; vitreous haemorrhage; registry:adverse_events

Suicidal ideation or behavior (2 lines; O35A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 3032	not stated; safety; suicidal ideation; registry:adverse_events
	A2	events				1 / 3031	not stated; safety; suicidal ideation; registry:adverse_events

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 3032	not stated; safety; registry:adverse_events
	A2	events				1 / 3031	not stated; safety; registry:adverse_events

Gastroparesis (2 lines; O37A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 3032	not stated; safety; diabetic gastroparesis; registry:adverse_events
	A2	events				1 / 3031	not stated; safety; diabetic gastroparesis; registry:adverse_events

Intestinal obstruction or ileus (4 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 3032	not stated; safety; ileus; registry:adverse_events
A1	events	1 / 3032	not stated; safety; intestinal obstruction; registry:adverse_events
A2	events	2 / 3031	not stated; safety; ileus; registry:adverse_events
A2	events	0 / 3031	not stated; safety; intestinal obstruction; registry:adverse_events

Pancreatic cancer (6 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	3 / 3032	not stated; safety; registry:adverse_events
A1	events	1 / 3032	not stated; safety; adenocarcinoma pancreas; registry:adverse_events
A1	events	1 / 3032	not stated; safety; pancreatic carcinoma metastatic; registry:adverse_events
A2	events	1 / 3031	not stated; safety; pancreatic carcinoma metastatic; registry:adverse_events
A2	events	0 / 3031	not stated; safety; adenocarcinoma pancreas; registry:adverse_events
A2	events	0 / 3031	not stated; safety; registry:adverse_events