| CTRI Number |
CTRI/2022/06/042973 [Registered on: 02/06/2022] Trial Registered Prospectively |
| Last Modified On: |
03/11/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Observational |
|
Type of Study
|
Case Control Study |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
Liver transplantation in patients with CirrHosis and severe Acute-on-Chronic Liver Failure |
|
Scientific Title of Study
|
Liver transplantation in patients with CirrHosis and severe Acute-on-Chronic Liver Failure (ACLF): iNdications and outComEs (CHANCE) Study on behalf of the EASL-CLIF Consortium |
| Trial Acronym |
CHANCE STUDY |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NCT04613921 |
ClinicalTrials.gov |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Mohamed Rela |
| Designation |
Chairman |
| Affiliation |
Dr Rela Institute and Medical Centre |
| Address |
Room No 101 Ground Floor,
Institute of Liver Disease and Transplantation
Dr. Rela Institute & Medical Centre
No 7 CLC Works Road
Chromepet
Chennai
Chennai
TAMIL NADU
600044
India |
| Phone |
00914466778888 |
| Fax |
00914466778889 |
| Email |
mohamed.rela@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Ashwin Rammohan |
| Designation |
Director of Academics |
| Affiliation |
Dr Rela Institute and Medical Centre |
| Address |
No 4066, 4th Floor
Institute of Liver Disease and Transplantation
No 7 CLC Works Road
Chromepet
Chennai
Chennai
TAMIL NADU
600044
India |
| Phone |
00914466778888 |
| Fax |
00914466778889 |
| Email |
ashwinrammohan@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Ashwin Rammohan |
| Designation |
Director of Academics |
| Affiliation |
Dr Rela Institute and Medical Centre |
| Address |
No 4066, 4th Floor
Institute of Liver Disease and Transplantation
No 7 CLC Works Road
Chromepet
Chennai
Chennai
TAMIL NADU
600044
India |
| Phone |
00914466778888 |
| Fax |
00914466778889 |
| Email |
ashwinrammohan@gmail.com |
|
|
Source of Monetary or Material Support
|
| EASLCLIF Consortium
Travessera de Grà cia, 11, Planta 7, 08021 Barcelona, B, Spain |
|
|
Primary Sponsor
|
| Name |
EASLCLIF Consortium |
| Address |
Travessera de Grà cia, 11, Planta 7, 08021 Barcelona, B, Spain |
| Type of Sponsor |
Research institution |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
Belgium
Brazil
Croatia
Czech Republic
Denmark
France
Germany
Hungary
India
Ireland
Italy
Netherlands
New Zealand
Portugal
Singapore
Slovenia
Spain
Turkey
United Kingdom
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| S Sudhindran |
Amrita Institute of Medical Science |
Ponekkara PO
Kochi
Ernakulam
KERALA |
04846681234
sudhisalini@icloud.com |
| Mohamed Rela |
Dr Rela Institute and Medical Centre |
Institute of Liver Disease and Transplantation
CLC Works Road
Chromepet
Chennai
TAMIL NADU |
00919677234320
mohamed.rela@gmail.com |
| Dr Samir Shah |
Global Hospitals Mumbai |
No 35 Dr Ernest Borges road opp
Shirodkar High School Parel East Parel Mumbai 12
Mumbai
MAHARASHTRA |
9820144338
02267670181
drshahsamir@gmail.com |
| Dharmesh Kapoor |
Yashoda Hospitals |
Raj Bhavan Road
Somajiguda
Hyderabad 500482
Hyderabad
TELANGANA |
04045674567
dharmesh_kapoor@hotmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Amrita Institute of Medical Science |
Approved |
| Ethics Committee For Biomedical and Health Research Global Hospitals Mumbai |
Approved |
| Institutional Ethics Committee |
Approved |
| Yashoda Hospital |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K746||Other and unspecified cirrhosis ofliver, |
|
|
Intervention / Comparator Agent
|
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
1. Male or female subject ≥18 years of age.
2. Subjects with diagnosis of liver cirrhosis (based on clinical, laboratory, endoscopic, and ultrasonographic features or on histology).
3. Subjects who have been hospitalized for acute decompensation of liver cirrhosis and referred to the transplant team:
Group 1: patients listed for liver transplantation with ACLF-2 or 3 at the time of listing or developing ACLF 2-3 while on the waiting list.
Group 2: patients listed for liver transplantation with decompensated cirrhosis without ACLF-2 or 3 and poor liver function (MELD>20) at the time of listing.
Group 3: patients having ACLF-2 or 3, are assessed for inclusion in the waiting list, but are finally not listed for liver transplantation.
4. Patients (or trusted person, family member or close relation if the patient is unable to express consent) who have been informed and signed their informed consent Inclusion criteria
|
|
| ExclusionCriteria |
| Details |
A subject meeting any of the following exclusion criteria is NOT eligible for participation in the study.
1. Acute or subacute liver failure without underlying cirrhosis.
2. Patients with hepatocellular carcinoma outside Milan criteria or other active neoplasia.
3. Subjects listed for transplantation other than liver or liver-kidney transplant.
4. Subjects with previous liver transplantation.
5. Vulnerable population (person under temporary or permanent guardianship or deprived of liberty by a judicial decision).
6. Pregnant and/or breastfeeding woman
7. Patients with relevant comorbidities that could impact the prognosis:
o Subjects with very severe hepatopulmonary syndrome (with PaO2 < 50 mmHg on FiO2 21%) or moderate to severe portopulmonary hypertension (non-reversible mPAP ≥ 35 mmHg or PVR ≥ 500 dyn.s.cm-5).
o Subjects with severe (grade IV) pulmonary disease (Global Obstructive Lung Disease [GOLD]).
o Subjects with chronic kidney disease requiring hemodialysis
o Subjects with severe heart disease (NYHA class III and IV)
o Subjects with a known infection with human immunodeficiency virus (HIV)
o Subjects with severe neurological or psychiatric disorders
8. Patients who cannot provide prior informed consent and when there is documented evidence that the patient has no legal surrogate decision maker and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent.
9. Physician and team not committed to provide intensive care if needed. |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To compare 1-year graft and patient survival rates after liver transplantation (LT) in patients with ACLF-2 or 3 at the time of LT with patients with decompensated cirrhosis without ACLF-2 or 3 at the time of LT and transplant-free survival of patients with ACLF-2 or 3 not listed for LT. |
1 year |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To assess the proportion of patients with ACLF-2 or 3 referred to transplant team who are listed or not and reasons of this decision.
|
1 year |
| To evaluate the outcomes of patients listed with ACLF-2 or 3 on the waiting list compared with those of patients listed with decompensated cirrhosis without ACLF-2 or 3. |
1 year |
To define independent predictive factors of death/delisting on the waiting list for patients listed with ACLF-2 or 3 and develop a new prognostic model based on ACLF criteria to predict mortality on the waiting list and to improve the allocation of organs.
|
1 year |
| To compare the characteristics of accepted grafts for patients listed with ACLF-2 or 3 with those of patients listed with decompensated cirrhosis without ACLF-2 or 3 and their impact on post-LT outcomes. |
1 year |
To explore independent predictive factors of death after LT for patients transplanted with ACLF-2 or 3 to design futility criteria for LT.
|
1 year |
| - To compare post-LT survival rates of patients with ACLF-2 or 3 at listing and patients without ACLF at listing who develop ACLF-2 or 3 on the waiting list. |
1 year |
| - To compare post-LT quality of life (QoL) for patients listed with ACLF-2 or 3 with those of patients listed with decompensated cirrhosis without ACLF-2 or 3. |
1 year |
| - To assess the resources utilization for patients listed with ACLF-2 or 3 (in intention-to-treat and per protocol) compared with patients listed with decompensated cirrhosis without ACLF-2 or 3. |
1 year |
|
|
Target Sample Size
|
Total Sample Size="3000"
Sample Size from India="500"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
05/06/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
05/06/2022 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
none yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Management of ACLF is mainly supportive. The poor outcomes lead physicians to consider liver transplantation as an option, even if controversial. In sicker recipients, LT results in immediate survival, but poor medium-term survival rates in some studies. The scarcity of deceased donors obliges to maximize LT success. Alternative strategies, as living-donor LT, should be explored. LDLT has impressive results in Eastern centers, but it is restrained in Western countries, due to potential life-threatening complications in the donor.
The aim of this study is to compare 1-year graft and patient survival rates after liver transplantation (LT) in patients with ACLF-2 or 3 at the time of LT, with patients with decompensated cirrhosis without ACLF-2 or 3 at the time of LT and also with transplant-free survival of patients with ACLF-2 or 3 not listed for LT. Secondary objectives are as follows: - To assess the proportion of patients with ACLF-2 or 3 referred to transplant team who are listed or not and reasons of this decision.
- To evaluate the outcomes of patients listed with ACLF-2 or 3 on the waiting list compared with those of patients listed with decompensated cirrhosis without ACLF-2 or 3.
- To define independent predictive factors of death/delisting on the waiting list for patients listed with ACLF-2 or 3 and develop a new prognostic model based on ACLF criteria to predict mortality on the waiting list and to improve the allocation of organs.
- To compare the characteristics of accepted grafts for patients listed with ACLF-2 or 3 with those of patients listed with decompensated cirrhosis without ACLF-2 or 3 and their impact on post-LT outcomes.
- To explore independent predictive factors of death after LT for patients transplanted with ACLF-2 or 3 to design futility criteria for LT.
- To compare post-LT survival rates of patients with ACLF-2 or 3 at listing and patients without ACLF at listing who develop ACLF-2 or 3 on the waiting list.
- To compare post-LT quality of life (QoL) for patients listed with ACLF-2 or 3 with those of patients listed with decompensated cirrhosis without ACLF-2 or 3.
|