EXpanded Combination of Evolocumab Plus Empagliflozin on Diabetes: EXCEED-BHS3 Trial

NCT03932721 | Completed Phase 4 DMC

• 1 other identifier: Exceed
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Based on the current evidence, empagliflozin could reduce cardiovascular morbidity and mortality in Diabetes Mellitus Type 2 (T2DM). Anti-PCSK9 therapy (evolocumab) can reduce the major cardiovascular events incidence in secondary prevention individuals, some of them presenting T2DM. The beneficial effect of the combined use of these two agents in T2DM remains unknown. Evaluating the effect of evolocumab on top of the best of care therapy for T2DM, including empaglifozin, on endothelial function may indicate the existence of some benefit related to cardiovascular outcomes.

Conditions

Dyslipidemia Associated With Type II Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypertension Arterial

Keywords

Dyslipidemia; Diabetes Mellitus, Type 2; Hypertension Arterial

Outcome Measures

Primary Outcomes (1)

• Difference in the percentage change in flow mediated dilation (FMD)

  Difference in the change in flow mediated dilation (FMD) between the randomization visit and at 16 weeks of treatment. Brachial artery measurements will be performed using a high-resolution ultrasound obtained by physicians with long experience in this exam. The FMD scan will be measured on Video clips recorded from 1 minute before cuff inflation to 5 minutes after deflation. Percentage change in diameter for FMD will be calculated in relation to the respective baseline scans.

  16 weeks

Secondary Outcomes (1)

• Difference in the percentage change in FMD reserve

  16 weeks

Other Outcomes (8)

• Difference in the change of plasma NO in mmol/L

  16 weeks

• Difference in the change of plasma VCAM-1 in pg/mL

  16 weeks

• Difference in the percentage change in FMD from randomization to 8 weeks of treatment.

  8 weeks

Study Arms (2)

Evolocumabe

ACTIVE COMPARATOR

Patients with T2DM treated with the standard of care (SGLT2 inhibitors, maximal statin dose and ideal control of blood glucose and blood pressure) AND evolocumab (anti-PCsk9).

Drug: Evolocumab 140 MG/ML

Control

NO INTERVENTION

Patients with T2DM treated exclusive with the standard of care (SGLT2 inhibitors, maximal statin dose and ideal control of blood glucose and blood pressure).

Interventions

Evolocumab 140 MG/ML DRUG

Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver's ability to remove LDL-C.

Also known as: Control

Evolocumabe

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• T2DM between 40 and 70 years old;
• Adequate glycemic control (HbA1c 7 to 9%) after run-in phase;
• Adequate blood pressure control (SBP ≤ 140 mm Hg)
• Maximal tolerated dose of statins and LDL-C between 70 and 100 mg/dL.

You may not qualify if:

• HbA1c \> 9% after run-in phase;
• Hospitalization for unstable angina or acute myocardial infarction within 6 months prior to enrolment;
• Acute stroke or transient ischemic attack (TIA) within 6 months prior to enrolment;
• Less than two months post coronary artery revascularization;
• BP ≥ 140 x 90 after anti-hypertensive medication adjustment;
• FMD \<2% or \> 10% at the time of randomization;
• Triglycerides \> 500 mg/dL;
• Known allergy to any of the study drugs;
• Severe coronary artery disease or heart failure;
• Systemic inflammation (C-reactive protein ≥ 5 mg/dL);
• Pregnancy or women during reproductive age;
• Active smoking or stopped smoking less than six months ago;
• Participation in other clinical studies or whose participation ended less than six months -ago.
• Use of SGLT2i or GLP-1a in the last sex months

Sponsors & Collaborators

• University of Campinas, Brazil: lead

Study Sites (1)

Centro de Pesquisa Clinica - FCM/Unicamp

Campinas, São Paulo, 13083-887, Brazil

Location

Related Publications (1)

• Breder I, Cunha Breder J, Bonilha I, Munhoz DB, Medorima STK, Oliveira DC, do Carmo HR, Moreira C, Kontush A, Zimetti F, Zanotti I, Carvalho LSF, Nadruz W, Muscelli E, Quinaglia T, Sposito AC; EXCEED-BHS3 Trial Investigator. Rationale and design of the expanded combination of evolocumab plus empagliflozin in diabetes: EXCEED-BHS3 trial. Ther Adv Chronic Dis. 2020 Sep 28;11:2040622320959248. doi: 10.1177/2040622320959248. eCollection 2020.

  PMID: 33062236 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypertension; Dyslipidemias

Interventions

evolocumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Andrei C Sposito, MD,Phd

  University of Campinas, Brazil

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinator of the Brazilian Heart Study Group

Model Details: Patients will be assigned to evolocumab (140 mg every two weeks) on top of the standard of care, SOC therapy ( SGLT2 inhibitors, maximal statin dose and ideal control of blood glucose (HbA1c 6.5% to 7%) and blood pressure (SBP \<140 mm Hg). Or to the exclusive use of the SOC therapy.

Study Record Dates

• First Submitted: April 12, 2019
• First Posted: May 1, 2019
• Study Start: October 1, 2018
• Primary Completion: June 30, 2021
• Study Completion: October 30, 2021
• Last Updated: March 9, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)