Study of Retatrutide on Patients with Heart and Kidney Diseases
Scientific Title of Study
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Event-Driven Study to Investigate the Effect of Retatrutide on the Incidence of Major Adverse Cardiovascular Events and the Decline in Kidney Function in Participants with Body Mass Index ≥27 kg/m2 and Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
J1I-MC-GZBO Version No. a, Protocol Date 05-JAN-2024
Protocol Number
NCT06383390
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Manish Mistry
Designation
Medical Director
Affiliation
Eli Lilly and Company (India) Pvt. Ltd.
Address
Plot No - 92, Sec - 32, Institutional Area, Gurgaon HARYANA-122001 India
Gurgaon HARYANA 122001 India
Phone
9820234897
Fax
Email
manish.mistry@lilly.com
Details of Contact Person Scientific Query
Name
Dr Manish Mistry
Designation
Medical Director
Affiliation
Eli Lilly and Company (India) Pvt. Ltd.
Address
Plot No - 92, Sec - 32, Institutional Area, Gurgaon HARYANA-122001 India
Gurgaon HARYANA 122001 India
Phone
9820234897
Fax
Email
manish.mistry@lilly.com
Details of Contact Person Public Query
Name
Dr Rajeev Sharan Shrivastava
Designation
Associate Director
Affiliation
Eli Lilly and Company (India) Pvt. Ltd.
Address
Plot No - 92, Sec - 32, Institutional Area, Gurgaon HARYANA-122001 India
Gurgaon HARYANA 122001 India
Phone
9810308697
Fax
Email
shrivastava_rajeev_sharan@lilly.com
Source of Monetary or Material Support
Eli Lilly and Company (India) PVT LTD, Plot No.92, Sector-32, Gurgaon, Haryana-122001
Primary Sponsor
Name
Eli Lilly Company India Pvt Ltd
Address
Eli Lilly and Company (India) PVT LTD, Plot No.92, Sector-32, Gurgaon, Haryana - 122001
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Australia Austria Belgium Brazil Canada Czech Republic Denmark France Germany Greece Hungary India Israel Italy Mexico Netherlands Poland Romania Slovakia Spain Turkey United Kingdom United States of America
Department of Cardiology, 44 Kingsway, Near Kasturchand Park, 2nd Floor, Room No. 208, Kingsway Hospital, Parwana Bhawan, Nagpur - 440001, Maharashtra, India Nagpur MAHARASHTRA
919320182115
drrvlohiya@gmail.com
Dr Prasad M Bhat
Life Care Hospital and Research Centre
2748/2152 M.L.N Enclave, 16th East Cross Road, 8thMain, D block, Sahakarnagara, Bangalore, Karnataka, India, 560092 Bangalore KARNATAKA
No. 85-86, Bangalore-Mysore Ring Road, Bannimantapa A Layout, Siddique Nagar, Mysore - 570015, Karnataka, India Mysore KARNATAKA
919900152852
cbkeshavamurthy@gmail.com
Dr Jai Shankar Krishnamoorthy
Medway Hospitals - Kodambakkam
2/26, 1st Main Road, Medway Heart Institute basement, Chennai, Tamil Nadu, India, 600024 Chennai TAMIL NADU
919455794557
drkjs68@yahoo.com
Dr Abhishek Sachdeva
Motilal Nehru Medical College Hospital
George Town, Allahabad, Uttar Pradesh, India, 211002 Allahabad UTTAR PRADESH
919990850478
sachdevadrabhishek@gmail.com
Dr Pritesh Parekh
Nirmal Hospital Private Limited
Ring road, Surat, Gujarat, India 395002 Surat GUJARAT
919824157137
parekh.cardiac.care@gmail.com
Dr Devendra Kumar Agarwal
Sardar Patel Medical College and A. G. Hospitals
Department of Cardiology, PBM Campus, Research Cell-B-Block, Ground Floor, Haldiram Moolchand Wing, Bikaner, Rajasthan, India, 334001 Bikaner RAJASTHAN
919829217899
tippy1234@rediffmail.com
Dr Atul Damodar Abhyankar
Shri Bachuhai Dahyabhai Mehta Mahavir Heart Institute
Ring Road, Shri B.D. Mehta Mahavir Heart Institute, Shree Mahavir Health Campus, Athwa gate, Surat, Gujarat, India, 395002 Surat GUJARAT
919825145738
atulda@hotmail.com
Dr Tanuj Bhatia
Shri Mahant Indiresh Hospital
Shri Guru Ram Rai Institute of Medical & Health Sciences, Patel Nagar, 4th Floor, Patel Nagar, Dehradun, Uttarakhand, India, 248001 Dehradun UTTARANCHAL
919936618283
tanujbhatia21@rediffmail.com
Dr Mahesh Chandumal Fulwani
Shrikrishna Hrudayalaya And Critical Care Center
Tikekar Road, Nagpur - 440012, Maharashtra, India Nagpur MAHARASHTRA
919921120005
drmaheshfulwani@gmail.com
Dr Kavita Tyagi
Sir Ganga Ram Hospital
Rajinder Nagar, Nephrology Research, Room No 1297, 2nd Floor, Old Rajinder Nagar, New Delhi, Delhi, India, 110060 New Delhi DELHI
Participants will receive placebo administered subcutaneously (SC) once weekly. The study will last for about 5 years.
Intervention
Retatrutide
Participants will receive escalated doses of retatrutide (from low to high doses) administered subcutaneously (SC) once weekly up to a maximum tolerated dose. The study will last for about 5 years.
Inclusion Criteria
Age From
45.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
- A Body Mass Index of more than 27.0 kilograms per meter squared.
- Participants may be with or without T2D unless their 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, or chronic kidney disease.
ExclusionCriteria
Details
- Have T1D or history of diabetic ketoacidosis.
- Have any of the following cardiovascular conditions 90 days or less, prior to randomization: myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or have New York Heart Association (NYHA) Classification Class 4 heart failure at screening.
- Have an eGFR less than 20 mL/min/1.73 meter squared or UACR more than 5000 mg/g at screening, or have received dialysis 90 days or less from the date of randomization, or have undergone a kidney transplant or have a scheduled transplant.
- Have had or plan to have a surgical treatment for obesity
- Have a history of chronic or acute pancreatitis, or history of medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) syndrome type 2, or have a clinically significant gastric emptying abnormality.
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
1. Time to First Occurrence of Composite Endpoints (includes nonfatal myocardial infarction (MI), nonfatal stroke, cardiovascular (CV) death, or hospitalization or urgent visit due to heart failure (HF)).
2. 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.
1. Randomization up to Study Completion (Approximate 248 Weeks)
2. Randomization up to Study Completion (Approximate 248 Weeks)
Secondary Outcome
Outcome
TimePoints
1. Time to First Occurrence of Composite Endpoint of Major Cardiovascular Events (MACE-3) (includes CV death, nonfatal MI, and nonfatal stroke).
2. Time to First Occurrence of Composite Endpoint of CV death, or hospitalization or urgent visit due to heart failure (HF).
3. Time to Occurrence of All-Cause Death.
4. Time to First Occurrence of composite endpoint of ≥ 40% Sustained Decline in eGFR, End-Stage Renal Disease (ESRD), or Renal Death.
5. Percentage change from Baseline in Albuminuria urinary albumin/creatinine ratio (UACR) in Participants with UACR ≥30 mg/g (0.03 mg/mg) at baseline.
1. Randomization up to Study Completion (Approximate 248 Weeks).
2. Randomization up to Study Completion (Approximate 248 Weeks).
3. Randomization up to Study Completion (Approximate 248 Weeks).
4. Randomization up to Study Completion (Approximate 248 Weeks).
5. Randomization up to Study Completion (Approximate 248 Weeks).
Target Sample Size
Total Sample Size="10000" Sample Size from India="530" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - YES
What data in particular will be shared? Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
What additional supporting information will be shared? Response - Study Protocol Response - Statistical Analysis Plan Response - Clinical Study Report
Who will be able to view these files? Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
For what types of analyses will this data be available? Response - For individual participant data meta-analysis.
By what mechanism will data be made available? Response (Others) - www.vivli.org
For how long will this data be available start date provided 01-10-2024 and end date provided 31-03-2025? Response - Beginning 3 months and ending 5 years following article publication.
Any URL or additional information regarding plan/policy for sharing IPD? Additional Information - NIL
Brief Summary
Retatrutide has the potential of demonstrating clinically meaningful improvements in long-term outcomes associated with obesity. The proposed Study GZBO is designed to characterize the effect of retatrutide on cardiovascular outcomes, kidney outcomes, and kidney function. The primary objectives of this trial are to assess the reduction of risk of the following events in participants with body mass index (BMI) of more than 27 kg/m2 and established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD):
- Incidence of cardiovascular (CV) events, including CV death, nonfatal myocardial infarction (MI), nonfatal stroke, or heart failure (HF) events that result in hospitalization or urgent visits.
- Incidence of kidney events, including end-stage kidney disease (ESKD), sustained decline of estimated glomerular filtration rate (eGFR) of more than 40%, CV death or renal death.