TERMINATED

Zibotentan and Dapagliflozin Combination, EvAluated in Liver Cirrhosis (ZEAL Study)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a two part Phase IIa/b multicentre, randomised, double-blind, placebo-controlled, parallel group dose-ranging study to assess the efficacy, safety, and tolerability of the combination of zibotentan and dapagliflozin, and dapagliflozin monotherapy versus placebo in participants with cirrhosis with features of portal hypertension.

Official Title

A Two Part Phase IIa/b Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Dose-ranging Study to Assess Efficacy, Safety, and Tolerability of the Combination of Zibotentan and Dapagliflozin, and Dapagliflozin Monotherapy Versus Placebo in Participants With Cirrhosis With Features of Portal Hypertension

Quick Facts

Study Start:2022-10-31

Study Completion:2025-07-17

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:TERMINATED

Study ID

NCT05516498

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
Age 18 years or older Willing and able to provide informed consent Able to understand and follow study procedures Stable medical condition	1. Any evidence of a clinically significant disease which in the investigator's opinion makes it undesirable for the participant to participate in the study. 2. Liver cirrhosis caused by chronic cholestatic liver disease 3. ALT or AST ≥ 150 U/L and/or total bilirubin ≥ 3 × ULN 4. Acute liver injury caused by drug toxicity or by an infection. 5. Any history of hepatocellular carcinoma. 6. Liver transplant or expected liver transplantation within 6 months of screening. 7. History of TIPS or a planned TIPS within 6 months from enrolment into the study. 8. Active treatment for HCV within the last 1 year or HBV antiviral therapy for less than 1 year. 9. Participants with T1DM. 1. INR \> 1.5. 2. Serum/plasma levels of albumin ≤ 35 g/L. 3. Platelet count \< 75 × 109/L. 4. History of ascites 5. History of hepatic hydrothorax 6. History of portopulmonary syndrome 7. History of hepatic encephalopathy 8. History of variceal haemorrhage 9. History of acute kidney injury 10. History of heart failure, including high output heart failure (eg, due to hyperthyroidism or Paget's disease) 1. INR \> 1.7. 2. Serum/plasma levels of albumin ≤ 28 g/L. 3. Platelet count \< 50 × /109L. 4. Acute kidney injury within 3 months of screening. 5. History of encephalopathy of West Haven grade 2 or higher within 6 months prior to screening. 6. History of variceal haemorrhage within 6 months prior to screening. 7. NYHA functional heart failure class III or IV or with unstable heart failure requiring hospitalisation for optimisation of heart failure treatment and who are not yet stable on heart failure therapy within 6 months prior to screening. 8. Heart failure due to cardiomyopathies that would primarily require specific other treatment: eg, cardiomyopathy due to pericardial disease, amyloidosis or other infiltrative diseases, cardiomyopathy related to congenital heart disease, primary hypertrophic cardiomyopathy, cardiomyopathy related to toxic or infective conditions (ie, chemotherapy, infective myocarditis, septic cardiomyopathy). 9. High output heart failure (eg, due to hyperthyroidism or Paget's disease). 10. Heart failure due to primary cardiac valvular disease/dysfunction, severe functional mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacement.

Inclusion Criteria

Exclusion Criteria

Age 18 years or older
Willing and able to provide informed consent
Able to understand and follow study procedures
Stable medical condition

1. Any evidence of a clinically significant disease which in the investigator's opinion makes it undesirable for the participant to participate in the study.
2. Liver cirrhosis caused by chronic cholestatic liver disease
3. ALT or AST ≥ 150 U/L and/or total bilirubin ≥ 3 × ULN
4. Acute liver injury caused by drug toxicity or by an infection.
5. Any history of hepatocellular carcinoma.
6. Liver transplant or expected liver transplantation within 6 months of screening.
7. History of TIPS or a planned TIPS within 6 months from enrolment into the study.
8. Active treatment for HCV within the last 1 year or HBV antiviral therapy for less than 1 year.
9. Participants with T1DM.
1. INR \> 1.5.
2. Serum/plasma levels of albumin ≤ 35 g/L.
3. Platelet count \< 75 × 109/L.
4. History of ascites
5. History of hepatic hydrothorax
6. History of portopulmonary syndrome
7. History of hepatic encephalopathy
8. History of variceal haemorrhage
9. History of acute kidney injury
10. History of heart failure, including high output heart failure (eg, due to hyperthyroidism or Paget's disease)
1. INR \> 1.7.
2. Serum/plasma levels of albumin ≤ 28 g/L.
3. Platelet count \< 50 × /109L.
4. Acute kidney injury within 3 months of screening.
5. History of encephalopathy of West Haven grade 2 or higher within 6 months prior to screening.
6. History of variceal haemorrhage within 6 months prior to screening.
7. NYHA functional heart failure class III or IV or with unstable heart failure requiring hospitalisation for optimisation of heart failure treatment and who are not yet stable on heart failure therapy within 6 months prior to screening.
8. Heart failure due to cardiomyopathies that would primarily require specific other treatment: eg, cardiomyopathy due to pericardial disease, amyloidosis or other infiltrative diseases, cardiomyopathy related to congenital heart disease, primary hypertrophic cardiomyopathy, cardiomyopathy related to toxic or infective conditions (ie, chemotherapy, infective myocarditis, septic cardiomyopathy).
9. High output heart failure (eg, due to hyperthyroidism or Paget's disease).
10. Heart failure due to primary cardiac valvular disease/dysfunction, severe functional mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacement.

Contacts and Locations

Study Locations (Sites)

Research Site

Birmingham, Alabama, 35233

United States

Research Site

Pasadena, California, 91105

United States

Research Site

San Francisco, California, 94115

United States

Research Site

West Hollywood, California, 90048

United States

Research Site

Rochester, Minnesota, 55905

United States

Research Site

Bronx, New York, 10467

United States

Research Site

Charleston, South Carolina, 29425

United States

Research Site

Dallas, Texas, 75246

United States

Research Site

Charlottesville, Virginia, 22903

United States

Research Site

Richmond, Virginia, 23249

United States

Research Site

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: AstraZeneca

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-10-31

Study Completion Date2025-07-17

Study Record Updates

Study Start Date2022-10-31

Study Completion Date2025-07-17

Terms related to this study

Additional Relevant MeSH Terms

Liver Cirrhosis