An European multinational study of a personalized approach of human albumin administration in patients with cirrhosis of the liver and complications

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Odense University Hospital, European Foundation For The Study Of Chronic Liver Failure

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

29 Mar 2023 → ongoing

Decision date (initial)

2023-02-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

European Union's Horizon 2020 research and innovation programme (no. 825694)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The overall objective is to validate the predictive biomarker of treatment response to human albumin therapy in patients with cirrhosis and ascites

Conditions and MedDRA coding

Liver cirrhosis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Decompensated liver cirrhosis defined as Child-Pugh score 7-12
2. Clinical and/or ultrasound evidenced ascites
3. Age above or equal to 18 years
4. At least five days since resolution of a decompensation event or any condition requiring hospitalization

Exclusion criteria 18

1. Patients with acute or subacute liver failure without underlying cirrhosis
2. Presence or history of severe extra-hepatic diseases (e.g., chronic renal failure requiring hemodialysis, severe heart disease (NYHA above grade II), severe chronic pulmonary disease (GOLD Score above or equal to grade C), severe neurological and psychiatric disorders, pulmonary arterial hypertension)
3. HIV positive or other condition associated with and/or requiring immunosuppression
4. Previous liver or other transplantation
5. Pregnancy
6. Breastfeeding
7. Patients who decline to participate, patients who cannot provide prior written informed consent due to other causes than hepatic encephalopathy or patients with hepatic encephalopathy who cannot provide prior written informed consent and when there is documented evidence that the patient has no legal surrogate decision maker or sufficient ability to provide delayed informed consent
8. Physician’s denial (investigator considers that the patient will not adhere to the study protocol scheduled, e.g. in case of heavy drinking)
9. Patients with cirrhosis who develop decompensation in the postoperative period following partial hepatectomy
10. Refractory ascites as defined by the International Ascites Club
11. Existing TIPS inserted <6 months ago
12. Portal vein thrombosis without signs of cavernous transformation or recanalization
13. Severe alcoholic hepatitis (Glasgow Alcoholic Hepatitis Score > 11)
14. Current, planned or previous treatment with direct antiviral agents for HCV in the last six months
15. Contraindications for human albumin infusion (pulmonary oedema, hypersensitivity etc.)
16. Evidence of current malignancy except for non-melanocytic skin cancer and hepatocellular carcinoma within BCLC-0 or BCLC-A
17. Hepatic encephalopathy grade III-IV
18. Participation in another study within 3 months prior to screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Cumulative number of liver-related clinical outcomes (variceal bleeding, ascites, spontaneous bacterial peritonitis, infection requiring hospitalization, acute kidney injury and overt hepatic encephalopathy) and TIPS (insertion or revision) with death and liver transplantation as counting and censoring events

Secondary endpoints 26

1. 6-months survival
2. The number of episodes of acute-on-chronic liver failures
3. Number of organ failures
4. Time-to-first liver-related clinical outcome
5. Patients’ quality of life
6. Time to first hospital admission (in days)
7. Number of hospital admissions
8. Days spent on hospitalization (in days)
9. Number of intensive care unit admissions
10. Length of intensive care unit admissions (in days)
11. Number of large volume paracentesis
12. Analysis of the cost/effectiveness ratio
13. Health economic evaluation
14. Changes in serum albumin levels
15. Number of treatment-related adverse events
16. Number of treatment-related serious adverse events
17. Signatures associated with a poor prognosis as defined by the Microb-Predict biomarker
18. Incidence of refractory ascites
19. Incidence of variceal bleeding
20. Incidence of spontaneous bacterial peritonitis
21. Incidence of infection requiring hospitalization
22. Incidence of acute kidney injury >= 1B
23. Incidence of hepatorenal syndrome acute kidney injury
24. Incidence of overt hepatic encephalopathy
25. Incidence of liver transplantation
26. Incidence of TIPS insertion or revision

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Odense University Hospital

Sponsor organisation

Odense University Hospital

Address

J B Winsloews Vej 4

City

Odense C

Postcode

5000

Country

Denmark

Scientific contact point

Organisation

Odense University Hospital

Contact name

Nikolaj Torp

Public contact point

Organisation

Odense University Hospital

Contact name

Nikolaj Torp

Third parties 1

European Foundation For The Study Of Chronic Liver Failure

Sponsor organisation

European Foundation For The Study Of Chronic Liver Failure

Address

Travessera De Gracia 11 7th Floor

City

Barcelona

Postcode

08021

Country

Spain

Sponsor responsibilities

Article 77 compliance

Odense University Hospital

Contact point sponsor

Odense University Hospital

Article 77 implementation

Odense University Hospital

Locations

7 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 33 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications