The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults Living With Obesity (TRIUMPH-Outcomes)

Phase 3

Recruiting

• Conditions: Atherosclerotic Cardiovascular Disease (ASCVD); Chronic Kidney Disease (CKD)
• Interventions: Drug: Placebo; Drug: Retatrutide

• Registration Number: NCT06383390
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The main purpose of this study is to determine if retatrutide can significantly lower the incidence of serious heart-related complications or prevent the worsening of kidney function. The trial will enroll adults with body mass index 27 kg/m\^2 or higher and Atherosclerotic Cardiovascular Disease and/or chronic kidney disease. The study will last for about 5 years. Participants will have up to 27 clinic visits with the study doctor.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-22
• Study First Submitted QC: 2024-04-22
• Study First Posted: 2024-04-25
• Study Start: 2024-04-30
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-05
• Last Update Posted: 2025-09-08
• Primary Completion: 2029-02
• Study Completion: 2029-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10000

Inclusion Criteria

• Participants may be without type 2 diabetes (T2D), or with T2D if their hemoglobin A1c (HbA1c) is 10% or lower

• Participants have established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD), as evidenced at least one of the following:

  • Coronary artery disease

  • Cerebrovascular disease

  • Peripheral arterial disease

  • Chronic kidney disease defined as:

    • eGFR <45 millilitres/minute/1.73 meter squared (mL/min/1.73m^2) and UACR >30 milligram/gram (mg/g) (0.030 mg/mg)
    • eGFR <60 mL/min/1.73 m^2 and UACR >100 mg/g (0.100 mg/mg), or
    • eGFR <75 mL/min/1.73 m^2 and UACR >300 mg/g (0.300 mg/mg) (eGFR is calculated by central lab based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin c equation as determined by central lab)

• A Body Mass Index of ≥27.0 kilograms per meter squared (kg/m^2)

Exclusion Criteria

Diabetes related:

• Participants have Type 1 Diabetes or any history of diabetic ketoacidosis

CV related:

• Participants have any of the following cardiovascular conditions ≤ 90 days prior to randomization:

  • Myocardial infarction
  • Acute coronary syndrome
  • Stroke, or
  • Coronary, peripheral, or carotid artery arterial revascularization procedure.

• Have acute decompensated heart failure requiring hospitalization.

• Have New York Heart Association (NYHA) Classification Class IV heart failure at screening

Kidney related:

• Participants have an eGFR <20 mL/min/1.73 m^2 at screening
• Have UACR >5000 mg/g (5.000 mg/mg) at screening
• Have received any form of dialysis ≤ 90 days from the date of randomization
• Have either undergone a kidney transplant or have a transplant procedure scheduled

Other medical conditions:

• Participants have had or plan to have a surgical treatment for obesity,
• Have a history of chronic or acute pancreatitis
• Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) syndrome type 2
• Have a known clinically significant gastric emptying abnormality, such as severe gastroparesis or gastric outlet obstruction

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive matching placebo administered SC.
Retatrutide	Retatrutide	Participants will receive escalated doses of retatrutide administered subcutaneously (SC) up to a maximum tolerated dose.

Primary Outcome Measures

Name	Time	Method
Time to First Occurrence of Composite Endpoints	Randomization up to Study Completion (Approximate 248 Weeks)	A composite endpoint includes nonfatal myocardial infarction (MI), nonfatal stroke, cardiovascular (CV) death, or hospitalization or urgent visit due to heart failure (HF).
Time to First Occurrence of Composite Endpoint of End Stage Kidney Disease (ESKD), ≥ 40% Sustained Decline in Estimated Glomerular Filtration Rate (eGFR), CV Death or Renal Death	Randomization up to Study Completion (Approximate 248 Weeks)	ESKD is defined as the following individual components: persistent eGFR \<15 mL/min/1.73 m\^2 confirmed by 2 measurements at least 4 weeks apart at the central laboratory, initiation of dialysis for at least 30 days, receiving a kidney transplant.; Sustained decline in eGFR (≥40%) will be confirmed by a repeated measure at least 4 weeks after the first result.

Secondary Outcome Measures

Name	Time	Method
Time to First Occurrence of Composite Endpoint of Major Cardiovascular Events (MACE-3)	Randomization up to Study Completion (Approximate 248 Weeks)	MACE-3 includes CV death, nonfatal MI, and nonfatal stroke.
Time to First Occurrence of Composite Endpoint of CV death, or hospitalization or urgent visit due to HF	Randomization up to Study Completion (Approximate 248 Weeks)	Time to First Occurrence of Composite Endpoint of CV death, or hospitalization or urgent visit due to HF.
Time to Occurrence of All-Cause Death	Randomization up to Study Completion (Approximate 248 Weeks)	Time to all-cause death.
Time to First Occurrence of composite endpoint of ≥ 40% Sustained Decline in eGFR, End-Stage Renal Disease (ESRD), or Renal Death	Randomization up to Study Completion (Approximate 248 Weeks)
Percentage change from Baseline in Albuminuria urinary albumin/creatinine ratio (UACR) in Participants with UACR ≥30 mg/g (0.03 mg/mg) at baseline	Randomization up to Study Completion (Approximate 248 Weeks)

Trial Locations

Locations (797)

Alabama Kidney Research; 🇺🇸 Alabaster, Alabama, United States

Central Research Associates; 🇺🇸 Birmingham, Alabama, United States

Alliance for Multispecialty Research, LLC; 🇺🇸 Norfolk, Virginia, United States

Nephrology Consultants; 🇺🇸 Huntsville, Alabama, United States

Prime Medical Group, LLC dba Gilbert Center for Family Medicine, LLC; 🇺🇸 Gilbert, Arizona, United States

Sun City Clinical Research; 🇺🇸 Glendale, Arizona, United States

Arizona Kidney Disease & Hypertension Center (AKDHC) - Thunderbird; 🇺🇸 Glendale, Arizona, United States

Helios Clinical Research - SAZ-PDV-026; 🇺🇸 Paradise Valley, Arizona, United States

Banner University Medical Center Phoenix; 🇺🇸 Phoenix, Arizona, United States

Phoenix Clinical LLC; 🇺🇸 Phoenix, Arizona, United States

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