NCT07165028ClinicalTrials.gov

A Master Protocol of Multiple Agents in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (SYNERGY-Outcomes)

A Master Protocol for a Randomized, Controlled, Clinical Trial of Multiple Pharmacologic Agents in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease Who Are at Increased Risk of Developing Major Adverse Liver Outcomes

RecruitingTaking participants now, according to the registry record.

Contact this study

In brief

Phase 34,500 participants sought563 sites34 countries

Registered in 1 registry

ClinicalTrials.govNCT07165028Open this record at ClinicalTrials.govSynced 2 weeks ago

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Trial information is shown as published by the registry, in its original language.

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How this study is set up

The points below are drawn from the public registry record for this study. Each one cites the field or sentence it came from. A dash (—) means the record does not state something — not that it is missing or wrong. Many well-run studies, especially small ones, leave some of these blank.

Present: Registered before enrolment beganFirst posted 2025-09-10; recorded start 2025-10-15
Present: Has a defined primary outcomeA primary outcome measure is listed in the record
Present: The primary outcome states a time frameThe primary outcome measure records a time frame
Present: Participants are randomly assignedAllocation is recorded as randomised
Present: Has a comparison groupThe record lists a placebo or comparator arm, or more than one study arm
Present: Uses blinding (masking)A masking level is recorded in the record
Not stated: An ethics committee is not stated in the registry recordThis registry's ingested record has no ethics-committee field
Not stated: Regulatory oversight (such as an IND or IDE) is not stated in the registry recordThis registry's ingested record has no regulatory-authorisation field
Not stated: A data monitoring committee is not stated in the registry recordThis registry's ingested record has no data-monitoring-committee fieldA data monitoring committee is not required for many smaller studies, and its absence here is not unusual.
Present: No cost to participants is mentioned in the recordChecked the summary, description and eligibility text; no cost-to-participant phrase found
Present: Sponsor has 347 other studies in this databaseCounted from the lead sponsor named in the record (Eli Lilly and Company)
Present: Sponsor has posted results for at least one studyBased on the sponsor’s studies in this database

The record lists 1 condition.
Lead sponsor type recorded as: industry.
Intervention regulatory context: investigational, within a phased regulatory pathway.

These are facts from the public registry record, not a judgement about the study. Discuss any trial with your own doctor before taking part.

What these facts mean, and what to ask · ruleset v1

Trial stature

Three independent measures of this study, described from its registry record — not a recommendation about it. A rigorous study by investigators nobody has heard of is better evidence than a weak study led by a famous one. How these are scored.

Methodological rigourSTRONG

A strong methodological design for a phase 3 study, judged from its ClinicalTrials.gov record.

How this score is built

Randomised allocation20/20
Participants are randomly allocated between arms
Blinding7/20
Single-blind
Control arm13/15
Placebo / sham control arm
Primary-outcome specificity10/10
Named primary outcome with a defined time frame
Endpoint type3/10
Surrogate or intermediate endpoint (conservative default)
Multi-centre8/8
Multi-centre: 563 sites
Data monitoring committee7/7
A data monitoring committee is in place
Prospective registration5/5
Registered before the study start date
Protocol / SAP posted0/5
No protocol or SAP posted to the registry

ScaleLARGE

A large study, international in scope: 4,500 participants (target), run at 563 sites, across 34 countries.

How this score is built

Enrolment35/40
4,500 participants (target)
Site count25/25
563 sites
Country count15/15
34 countries
Planned duration10/10
Planned over about 83 months
Sponsor scale9/10
Eli Lilly and Company has led 326 trials in our corpus

Investigator standingUNKNOWN

We have no verifiable track record for the investigator named on this trial. That is common for early-career investigators and for records held outside ClinicalTrials.gov — it is not a negative signal.

How this score is built

Investigator standing0/100
No investigator recorded in the registry for this trial

These describe the registry record only, and today we hold ClinicalTrials.gov data. Absent fields lower a score, and absence often reflects registration practice rather than study quality. A high-stature trial is not necessarily safer or a better choice for you — enrolling in a large definitive trial can mean a higher chance of receiving placebo, while a small early-phase study may be the only route to a new therapy.

Summary

The main purpose of the SYNERGY-OUTCOMES study is to find out whether retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in people with high-risk metabolic dysfunction-associated steatotic liver disease (MASLD). The study will enroll adults who have MASLD based on non-invasive tests (NITs), which indicate they are more likely to develop MALO. Participants will be randomly assigned within a Master Protocol to receive either retatrutide (N1T-MC-RT01), tirzepatide (N1T-MC-TZ01) or placebo. The trial plans to enroll about 4,500 adults and will run for approximately 224 weeks. Participants may have up to approximately 25 to 30 clinic visits throughout the study to monitor their health, complete study procedures, and assess liver function and disease progression. Once the study is complete, eligible participants may participate in an optional 2-year extension study, in which all participants will receive either retatrutide or tirzepatide, even if they received placebo in the main study.

Conditions

Metabolic Dysfunction-Associated Steatotic Liver Disease

Eligibility

Eligibility
Sex	All
Ages	18 Years – No maximum
Healthy volunteers	No

Eligibility as written in the registry

Inclusion Criteria: * Have liver fat content ≥8% * Have ELF score of ≥9 and ≤10.8 at screening * Have VCTE LSM ≥10 kilopascal (kPa) and \<20 kPa at screening Exclusion Criteria: * Have any other type of liver disease other than MASLD * Have a body mass index (BMI) \<25 kilogram per square meter (kg/m2) * Prior decompensated liver disease (history of esophageal/gastric varices, ascites, hepatic encephalopathy) * Have lost more than 11 pounds within the 3 months prior to screening * Have a hemoglobin A1c (HbA1c) greater than 10% * Have type 1 diabetes

Eligibility in plain statements

This record's criteria have not been broken into separate statements yet. The registry text above is complete and is the authoritative version.

Study design

Study design
Study type	Interventional
Phase	Phase 3
Allocation	Randomised
Intervention model	PARALLEL
Primary purpose	TREATMENT
Masking	SINGLE (1)
Enrolment	4,500 participants sought

Sponsor and collaborators

Eli Lilly and Company Sponsor

Arms and interventions

Tirzepatide (TZ01)EXPERIMENTAL
Participants will receive tirzepatide subcutaneously (SC)
Placebo (TZ01)PLACEBO_COMPARATOR
Participants will receive placebo SC
Retatrutide (RT01)EXPERIMENTAL
Participants will receive retatrutide SC
Placebo (RT01)PLACEBO_COMPARATOR
Participants will receive placebo SC

Interventions

Drug Placebo
Administered SC
Drug Retatrutide
Administered SC
Drug Tirzepatide
Administered SC

Outcome measures

Primary outcome
Time to First Occurrence of Any Component of the Composite Endpoint for Major Adverse Liver Outcomes (MALO)
Composite endpoint comprised of progression to cirrhosis, development of large esophageal varices, gastric varices or development of varices needing treatment, development of ascites, development of hepatic encephalopathy, evidence of active or recent variceal hemorrhage, increase in model for end-stage liver disease (MELD) from ≤12 to ≥15, liver transplantation, all-cause mortality
Time frame Baseline up to Study Completion (about 224 weeks)
Secondary outcome
Change from Baseline in Enhanced Liver Fibrosis (ELF) Score
Time frame Baseline, Week 104
Secondary outcome
Change from Baseline in Vibration-Controlled Transient Elastography Liver Stiffness Measurement (VCTE LSM)
Time frame Baseline, Week 104
Secondary outcome
Percent Change from Baseline in Liver Fat Content (LFC)
Time frame Baseline, Week 104
Secondary outcome
Time to Occurrence of Progression to Cirrhosis
Time frame Baseline up to Study Completion (about 224 weeks)
Secondary outcome
Change from Baseline in Aspartate Aminotransferase (AST)
Time frame Baseline, Study Completion (about 224 weeks)
Secondary outcome
Change from Baseline in Alanine Aminotransferase (ALT)
Time frame Baseline, Study Completion (about 224 weeks)
Secondary outcome
Change from Baseline in Body Weight
Time frame Baseline, Study Completion (about 224 weeks)
Secondary outcome
Change from Baseline in Non-Alcoholic Steatohepatitis-CHECK Score (NASH-CHECK)
Time frame Baseline, Week 104
Secondary outcome
Time to First Occurrence of Any Component Event of the Composite Endpoint of Major Adverse Cardiovascular Events (MACE-3)
MACE-3 composite endpoint includes nonfatal myocardial infarction, nonfatal stroke, cardiovascular death
Time frame Baseline up to Study Completion (about 224 weeks)

Dates

Dates
Start date	October 15, 2025 (actual)
Primary completion	August 1, 2030 (estimated)
Completion	August 1, 2032 (estimated)
First posted	September 10, 2025 (actual)
Last updated	September 8, 2026
Results posted	Not stated in the registry record
Status last verified	September 2026

Actual means the event happened. Estimated means the sponsor expects it. The two mean different things.

Locations

481 sites are recruiting

Argentina

Argentina
Facility	City	Status
Hospital Italiano de Buenos Aires	ABB	Recruiting
CIPREC	Buenos Aires	Recruiting
Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada	Buenos Aires	Recruiting
Mautalen Salud e Investigación	Buenos Aires	Recruiting
Centro Médico Viamonte	Buenos Aires	Recruiting
Centro de Investigaciones Metabólicas (CINME)	Buenos Aires	Recruiting
Glenny Corp. S.A.	Buenos Aires	Recruiting
Cicemo Srl	Buenos Aires	Recruiting
DOM Centro de Reumatología	Buenos Aires	Recruiting
Fundación Respirar	Buenos Aires	Recruiting
Instituto de Investigaciones Clínicas Córdoba	Córdoba	Recruiting
Centro de Investigaciones Clínicas Baigorria	Granadero Baigorria	Recruiting
Instituto de Investigaciones Clínicas Mar del Plata	Mar del Plata	Recruiting
DIM Clínica Privada	Ramos Mejía	Recruiting
INECO Neurociencias Oroño	Rosario	Recruiting
Instituto de Investigaciones Clinicas Rosario	Rosario	Recruiting
Centro de Diagnóstico y Rehabilitación (CEDIR)	Santa Fe	Recruiting

Australia

Australia
Facility	City	Status
Flinders Medical Centre	Adelaide	Recruiting
Nightingale Research	Adelaide	Recruiting
Box Hill Hospital	Box Hill	Recruiting
Royal Brisbane and Women's Hospital	Brisbane	Recruiting
Core Research Group	Brisbane	Recruiting
Mater Misericordiae Limited	Brisbane	Recruiting
Gallipoli Medical Research Ltd	Brisbane	Recruiting
Genesis Research Services	Broadmeadow	Recruiting
Barwon Health	Geelong	Not yet recruiting
Austin Health	Heidelberg	Recruiting
Ipswich Hospital	Ipswich	Recruiting
Fiona Stanley Hospital	Murdoch	Recruiting
TrialsWest - Osborne Park	Osborne Park	Recruiting
The Royal Melbourne Hospital	Parkville	Recruiting
Gold Coast University Hospital	Southport	Recruiting
Westmead Hospital	Westmead	Recruiting

Austria

Austria
Facility	City	Status
Medizinische Universität Graz	Graz	Recruiting
Uniklinikum Salzburg	Salzburg	Recruiting
Klinik Landstraße	Vienna	Recruiting
Medizinische Universität Wien	Vienna	Recruiting
Landesklinikum Wiener Neustadt	Wiener Neustadt	Not yet recruiting

Belgium

Belgium
Facility	City	Status
UZ Brussel	Brussels	Not yet recruiting
Centre Hospitalier Universitaire Brugmann	Brussels	Recruiting
Université Libre de Bruxelles - Hôpital Erasme	Brussels	Not yet recruiting
Cliniques universitaires Saint-Luc	Brussels	Not yet recruiting
Antwerp University Hospital	Edegem	Not yet recruiting
AZ Maria Middelares	Ghent	Recruiting
UZ Gent	Ghent	Not yet recruiting
AZ Groeninge Campus Kennedylaan	Kortrijk	Not yet recruiting
AZ Oostende vzw	Ostend	Recruiting
AZ Delta vzw	Roeselare	Recruiting
VITAZ	Sint-Niklaas	Not yet recruiting

Brazil

Brazil
Facility	City	State or region	Status
NewData Clinical Research - Aracaju	Aracaju		Recruiting

513 further sites are listed in the registry record.

Study documents

No documents are linked in this registry record.

Changes over time

September 8, 2026
Site removed
2 sites removed (563 total)
565563
August 21, 2026
Site added
1 site added (565 total)
564565
August 6, 2026
Site added
1 site added (564 total)
563564

Registry: ClinicalTrials.gov · NCT########

https://xmedica.io/trials/ctgov/NCT07165028

Categories

Registered in 1 registry

Interested in this study?

How this study is set up

Summary

Conditions

Eligibility

Eligibility as written in the registry

Eligibility in plain statements

Study design

Sponsor and collaborators

Arms and interventions

Interventions

Outcome measures

Dates

Locations

Argentina

Australia

Austria

Belgium

Brazil

Study documents

Changes over time