Acute-On-Chronic Liver FailurePhase 1TRUSTNCT03737448
TRimetazidine for acUte on Chronic Liver Failure STudy
A Phase 1 study testing Trimetazidine in people with Acute-On-Chronic Liver Failure, run by Martin Pharmaceuticals at 24 sites in 5 countries.
Trial summary
The study will assess the pharmacokinetics (PK), tolerability, and safety of oral trimetazidine administered to subjects with AD (ACLF Grade 0) or with ACLF Grade 1 or 2. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute-On-Chronic Liver Failure
- What is being tested?
- Trimetazidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 24 sitesin 5 countries
- Study dates
- 28 Nov 2018to 30 Jun 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
24 sites in 5 countries.
24 sites in 5 countries
Spain8 sites
Hospital Clinic
Barcelona
Hospital Valle de Hebron
Barcelona
Hospital Reina Sofia
Córdoba
Hospital Gregorio Marañón
Madrid
Hospital Puerta de Hierro
Madrid
Hospital Ramon y Cajal
Madrid
Hospital Marques de Valdecilla Santander
Santander
Hospital Virgen del Rocio
Seville
Germany7 sites
University of Essen
Essen
JW Goethe Clinic
Frankfurt
Universitätsklinikum Halle Klinik und Poliklinik für Innere Medizin I
Halle
University of Hannover
Hanover
University of Heidelberg
Heidelberg
University of Leipzig
Leipzig
University of Münster
Münster
France4 sites
Hospital Claude Huriez
Lille
Hospital Pitie-Salpetriere
Paris
Rennes University Hospital
Rennes
Hôpital Paul Brousse
Villejuif
Austria3 sites
Medical University of Graz
Graz
Medical University of Innsbruck
Innsbruck
Medical University of Vienna
Vienna
About this study
Official title: A Phase 1b Open-Label Study Assessing the Pharmacokinetics, Tolerability, and Safety of Oral Trimetazidine in Subjects With Acute-on-Chronic Liver Failure
The study will assess the pharmacokinetics (PK), tolerability, and safety of oral trimetazidine administered to subjects with AD (ACLF Grade 0) or with ACLF Grade 1 or 2.
Read the detailed description
The study will assess the PK, tolerability, and safety of oral trimetazidine administered to subjects with acute-on-chronic (ACLF) Grades 1 and 2 with liver failure and a range of renal function. Subjects will receive up to 60 mg/day for 28 days.
Two groups of subjects will be enrolled:
Group 1
- 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.
Group 2
- 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).
- Conditions
- Acute-On-Chronic Liver Failure
- Being tested
- Trimetazidine
- Medical subject headings
- Acute-On-Chronic Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrimetazidineDrug
Subjects with receive up to 60 mg daily
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | * 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. Receives: Drug: Trimetazidine |
| Group 2 | Experimental | * 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). Receives: Drug: Trimetazidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
plasma pharmacokinetics
Cmax
Measured: 28 days
plasma pharmacokinetics
AUC
Measured: 28 days
Secondary outcomes (1)
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Adverse events
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2018
- Study start28 Nov 2018
- Primary completion30 Jun 2021 (estimated)
- Study completion30 Jun 2021 (estimated)
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute-On-Chronic Liver FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Martin Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer, Study director, Martin Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03737448
- Sponsor's protocol ID
- MP-0614-001
- Acronym
- TRUST
- Status last verified
- Mar 2021
- First submitted
- 7 Nov 2018
- Last updated
- 4 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Open-Label Study Assessing the Pharmacokinetics, Tolerability, and Safety of Oral Trimetazidine in Subjects With Acute-on-Chronic Liver Failure
- ClinicalTrials.gov ID
- NCT03737448
- Acronym / sponsor ID
- TRUST / MP-0614-001
- Conditions
- Acute-On-Chronic Liver Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Lack of enrollment
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Martin PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 28 Nov 2018 (actual)
- Primary completion
- 30 Jun 2021 (estimated)
- Study completion
- 30 Jun 2021 (estimated)
- First posted
- 9 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will assess the pharmacokinetics (PK), tolerability, and safety of oral trimetazidine administered to subjects with AD (ACLF Grade 0) or with ACLF Grade 1 or 2.
Detailed description
The study will assess the PK, tolerability, and safety of oral trimetazidine administered to subjects with acute-on-chronic (ACLF) Grades 1 and 2 with liver failure and a range of renal function. Subjects will receive up to 60 mg/day for 28 days.
Two groups of subjects will be enrolled:
Group 1
- 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.
Group 2
- 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).
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Trimetazidine* 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. |
| Group 2 | Experimental | Drug: Trimetazidine* 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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:
- For Group 2:
Key exclusion criteria (25 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrimetazidineSubjects with receive up to 60 mg daily | Drug | Group 1, Group 2 |
Primary outcome
plasma pharmacokinetics
Time frame: 28 days
Cmax
plasma pharmacokinetics
Time frame: 28 days
AUC
1 secondary outcome
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Time frame: 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chief Medical Officer study director
Martin Pharmaceuticals
24 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Trimetazidine in people with Acute-On-Chronic Liver Failure, run by Martin Pharmaceuticals at 24 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 4 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Spain, Germany, France, Austria, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
plasma pharmacokinetics (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2021.