This Study Combines Data From 3 Other Studies Testing Empagliflozin in Patients With Diabetes or With Chronic Heart Failure. The Study Looks at the Numbers of Patients Who Had Lower Limb Amputations

NCT04937816 | Completed Results FDA Drug

• 1 other identifier: 1245-0171
• Study Type: observational
• Target: 16,746
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this exploratory meta-analysis is to evaluate the frequencies, incidence rates, and hazard ratios of lower-limb amputation (LLA) events (primary outcome) and of adverse events related to amputation (secondary outcome) in patients treated with empagliflozin compared with placebo in the pooled population of the long-term studies 1245.25, 1245.110, and 1245.121 (SAF-M1), in the pooled population of studies 1245.110 and 1245.121 (SAFM2), and in each of the 3 studies separately.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Incidence Rate of Lower Limb Amputation (LLA)

  Incidence rate of lower limb amputation (LLA). Incidence rate were provided as rate per 100 patients-years (pt-yrs) calculated as the observed number of patients with event divided by observed time-at-risk over all patients. Time at risk was derived as followed: Patient with event: time at risk in days = date of start of first event - treatment start date + 1. Patients without event: time at risk in days = last date on treatment + 7 days - treatment start date + 1. Abbreviation: pt-yrs = patient-years.

  From first to last dose of study medication plus 7 days to account for the residual drug effect, up to 1639 days.

Secondary Outcomes (1)

• Incidence Rate of Adverse Events Related to Amputation

  From first to last dose of study medication plus 7 days to account for the residual drug effect, up to 1639 days.

Study Arms (7)

EMPA-REG - Placebo

Participants of the EMP-REG OUTCOME study (1245.25) who received placebo.

Drug: Placebo

EMPA-REG - Empagliflozin low dose

Participants of the EMPA-REG OUTCOME study (1245.25) who received a low dose of empagliflozin once daily (QD).

Drug: Empagliflozin

EMPA-REG - Empagliflozin high dose

Participants of the EMP-REG OUTCOME study (1245.25) who received a high dose of empagliflozin once daily (QD).

Drug: Empagliflozin

EMPEROR-Preserved - Empagliflozin

Participants of the EMPEROR-Preserved study (1245.110) who received empagliflozin once daily (QD).

Drug: Empagliflozin

EMPEROR-Preserved - Placebo

Participants of the EMPEROR-Preserved study (1245.110) who received placebo once daily (QD).

Drug: Placebo

EMPEROR-Reduced - Empagliflozin

Participants of the EMPEROR-Reduced study (1245.121) who received empagliflozin once daily (QD).

Drug: Empagliflozin

EMPEROR-Reduced - Placebo

Participants of the EMPEROR-Reduced study (1245.121) who received placebo once daily (QD).

Drug: Placebo

Interventions

Placebo DRUG

Placebo

EMPA-REG - Placebo; EMPEROR-Preserved - Placebo; EMPEROR-Reduced - Placebo

Empagliflozin DRUG

Empagliflozin once daily

EMPA-REG - Empagliflozin high dose; EMPA-REG - Empagliflozin low dose; EMPEROR-Preserved - Empagliflozin; EMPEROR-Reduced - Empagliflozin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with type 2 diabetes mellitus and increased cardiovascular risk (1245.25), patients with chronic heart failure with preserved ejection fraction (1245.110), and patients with chronic heart failure with reduced ejection fraction (1245.121), who were either treated with empagliflozin or placebo.

You may qualify if:

• Age ≥18 years, diagnosis of type 2 diabetes mellitus (T2DM)
• Drug-naïve or pretreated with any background therapy
• Glycated haemoglobin (HbA1c) criteria
• Patients who were drug-naïve: HbA1c of 7 to 10%
• Patients with background therapy: HbA1c of 7 to 9%
• Body mass index (BMI) ≤45 kg/m2
• With high cardiovascular risk, defined as ≥1 of the following criteria
• History of myocardial infarction (\>2 months prior to enrollment)
• Multi-vessel coronary artery disease: ≥2 major vessels or left main coronary artery
• Single-vessel coronary artery disease with no scheduled revascularization/previously unsuccessful revascularization
• Hospital discharge due to unstable angina pectoris (\>2 months prior to enrollment)
• History of stroke (\>2 months prior to enrollment)
• Peripheral occlusive arterial disease
• Age ≥18 years (Japan, age ≥20 years)
• Chronic heart failure (HF) new york hear association (NYHA) class II to IV

You may not qualify if:

• Uncontrolled hyperglycemia: fasting plasma glucose \>240 mg/dl
• Severe renal impairment defined as eGFR \<30 ml/min by Modification of diet in renal disease (MDRD) formula
• Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial, or participating in another trial (involving an investigational drug and/or follow-up)
• Myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or transient ischaemic attack ≤90 days before screening
• Heart transplant recipient, or listed for heart transplant
• Acute decompensated HF
• Systolic blood pressure (SBP) ≥180 mmHg at randomisation
• Symptomatic hypotension and/or SBP \<100 mmHg at screening or randomisation
• Impaired renal function defined as Estimated glomerular filtration rate (eGFR) Chronic Kidney Disease Epidemiology Collaboration Equation (based on serum creatinine value) \<20 ml/min/1.73 m2 or requiring dialysis at screening

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Boehringer Ingelheim

Ingelheim, 55218, Germany

Location

Related Links

• Related Info

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

For study NCT01131676, events leading to LLA were not prespecified but were identified during unblinded medical review of data. Also, since both empagliflozin arms (10 and 25 mg) of study NCT01131676 were combined for the pooled SAF-M1 analysis, this led not only to a different sample size, but also to different patient populations for placebo and empagliflozin, respectively.

Results Point of Contact

• Title: Boehringer Ingelheim
• Organization: Boehringer Ingelheim, Call Center

clintriage.rdg@boehringer-ingelheim.com

018002430127

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: June 24, 2021
• Study Start: June 1, 2021
• Primary Completion: July 13, 2021
• Study Completion: July 13, 2021
• Last Updated: February 8, 2024
• Results First Posted: February 8, 2024

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)