TRimetazidine for acUte on Chronic Liver Failure STudy (TRUST)
Acute-On-Chronic Liver Failure
About this trial
This is an interventional other trial for Acute-On-Chronic Liver Failure
Eligibility Criteria
Inclusion Criteria:
- Age 18 to 75 years, inclusive, at screening.
- Stable diagnosis of AD, ACLF Grade 1 or ACLF Grade 2 for no less than 2 days (as determined at the discretion of the investigator)*.
- Anticipated duration of hospital stay of at least 7 days.
For Group 1:
- AD with SCr ≥ 1 and < 2 mg/dL, OR
ACLF 1 with
- Tbil ≥ 12 mg/dL, SCr ≥ 1.5 and < 2 mg/dl, and HE 0-2, or
- Tbil ≥ 12 mg/dL, and SCr < 1.5 mg/dL, and HE 1-2, or
- INR ≥ 2.5, SCr ≥ 1.5 and < 2 mg/dl, and HE 0-2, or
- INR ≥ 2.5, SCr < 1.5 mg/dL, and HE 1-2, OR
ACLF 2 with
- Tbil ≥ 12 mg/dL, INR ≥ 2.5, and SCr < 2 mg/dL, or
- Tbil ≥ 12 mg/dL, HE 3-4, and SCr < 2 mg/dL
For Group 2:
- ACLF 1 with SCr ≥ 2.0 and < 3.5 mg/dL, OR
ACLF 2 with
- Tbil ≥ 12 mg/dL, and SCr ≥ 2 and < 3.5 mg/dL, or
- INR ≥ 2.5, and SCr ≥ 2 and < 3.5 mg/dL.
- Female patients must be of non-childbearing potential, or, if non-sterile, must agree to sexual abstinence or use a highly effective method of contraception from Screening to 3 days after the final dose.
- Non sterile male patients must agree to sexual abstinence or use a highly effective method of contraception from Screening to 3 days after the final dose if sexually active.
- Able to comprehend and willing to sign an informed consent form, or, if unable to consent, consent is conducted per local requirements.
Exclusion Criteria:
- Diagnosis of AD or ACLF (of any grade) >14 days before enrollment*.
- Circulatory failure.
- Respiratory failure i.e. PaO2/FiO2 ≤ 200 and/or baseline SpO2/FiO2 ≤ 214.
- Brain failure (West Haven grade 3 or 4 hepatic encephalopathy) with coagulation failure (INR > 2.5).
- Gastrointestinal bleeding within 72 hours prior to enrollment. (Subjects who fail this criterion may qualify after 72 hours).
- Uncontrolled bacterial infection (urinary tract infection, spontaneous bacterial peritonitis, pneumonia, bacteremia, soft tissue infections, etc.) (as determined at the discretion of the investigator).
- Invasive fungal infection.
- Platelet count <30,000 cells/mL.
- White blood cell count <1000 cells/uL.
- Patients on hemodialysis or continuous venovenous hemofiltration.
- Patients who have undergone or are scheduled for imminent organ transplantation. (Patients may be on a transplant list as long as no date has been set for transplantation)
- Hospitalization for ACLF within the 3 months prior to screening.
- History of hepatocellular carcinoma, unless within Milan Criteria (up to 3 lesions each < 3 cm or 1 lesion < 5 cm; no extrahepatic involvement; no evidence of gross vascular invasion).
- Active non-hepatic malignancy.
- Parkinson's disease, Parkinsonian-type symptoms (gait disorder, tremor, etc.), restless leg syndrome or other movement disorders other than asterixis.
- Fulminant Wilson's, fulminant autoimmune hepatitis, or Budd-Chiari syndrome.
- Septic shock (hypotension requiring vasopressors to maintain a mean arterial pressure of 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L (> 18 mg/dL) after adequate fluid resuscitation.
- Patients who have undergone placement of a transjugular intrahepatic portosystemic shunt (TIPS) or surgical shunt in the past 6 months.
- Any invasive procedure within 48 hours prior to enrollment with high risk of uncontrolled bleeding (as determined at the discretion of the investigator).
- Female with a positive pregnancy test or lactating.
- Positive results for human immunodeficiency virus HIV-1 or HIV-2.
- Current treatment with trimetazidine.
- Known allergy to trimetazidine or excipients.
- Currently receiving an investigational treatment.
- Any condition that, in the opinion of the Investigator (or designee), would limit the subject's ability to complete or participate in this clinical study.
Sites / Locations
- Medical University of Graz
- Medical University of Innsbruck
- Medical University of Vienna
- University of Antwerp
- Erasme Hospital
- Hospital Claude Huriez
- Hospital Pitie-Salpetriere
- Rennes University Hospital
- Hôpital Paul Brousse
- University of Essen
- JW Goethe Clinic
- Universitätsklinikum Halle Klinik und Poliklinik für Innere Medizin I
- University of Hannover
- University of Heidelberg
- University of Leipzig
- University of Münster
- Hospital Clinic
- Hospital Valle de Hebron
- Hospital Reina Sofia
- Hospital Gregorio Marañón
- Hospital Puerta de Hierro
- Hospital Ramon y Cajal
- Hospital Marques de Valdecilla Santander
- Hospital Virgen del Rocio
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Group 1
Group 2
AD with serum creatinine ≥ 1 and < 2 mg/dL, OR ACLF 1 with liver failure and serum creatinine ≥ 1.5 and < 2 mg/dl, or liver failure and West Haven grade 1-2 hepatic encephalopathy, or coagulation failure and serum creatinine ≥ 1.5 and < 2 mg/dl, or coagulation failure and West Haven grade 1-2 hepatic encephalopathy, OR ACLF 2 with liver failure and coagulation failure, or liver failure and West Haven grade 3-4 hepatic encephalopathy.
ACLF 1 with renal failure (serum creatinine ≥ 2.0 and < 3.5 mg/dL), OR ACLF 2 with liver failure and renal failure (serum creatinine ≥ 2.0 and < 3.5 mg/dL), or coagulation failure and renal failure (serum creatinine ≥ 2.0 and < 3.5 mg/dL).