Liver CirrhosisPRECISENCT07750587
Predicting Response and Exposure Changes in Cirrhosis for Effectiveness
A study testing Five-Drug CYP Probe Cocktail in people with Liver Cirrhosis, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
Trial summary
The goal of this clinical trial is to learn how liver cirrhosis affects the way the body processes drugs in adults with different stages of liver cirrhosis. This information may help improve drug dosing for people with liver cirrhosis in the future. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Cirrhosis
- What is being tested?
- Five-Drug CYP Probe Cocktail
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2026to 1 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Clinical, radiological and/or histological diagnosis of cirrhosis
- Informed consent signed prior to participation in the study
Who cannot join
- Original MELD score > 30
- Estimated creatinine clearance < 30 mL/min, calculated by using the Cockcroft-Gault equation
- Known poor metaboliser status for one of the CYP enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A) described in the medical record
- Previous clinically relevant adverse reaction or intolerance to one of the drugs in the probe drug cocktail
- Recent exposure to one of the drugs in the drug probe cocktail within five elimination half-lives prior to drug administration (corresponding to approximately 1-10 days depending on the probe drug)36-40:
- caffeine: 5h x 5 = 25 hours
Show all 19Show fewer
- warfarin: 50h x 5 = 250 hours
- esomeprazole: 1.3h x 5 = 6.5 hours
- metoprolol: 3.5h x 5 = 17.5 hours
- midazolam: 2.5h x 5 = 12.5 hours
- Absolute contraindication for one of the drugs in the probe drug cocktail36-40:
- caffeine: drug hypersensitivity
- warfarin: drug hypersensitivity and active bleeding
- esomeprazole: drug hypersensitivity, congenital long QT syndrome and suspected gastrointestinal malignancy
- metoprolol: drug hypersensitivity, cardiogenic shock, second- and third degree AV block, bradycardia (< 50 beats per minute), sick sinus syndrome including SA block, symptomatic hypotension (mean arterial pressure < 65 mmHg), metabolic acidosis and untreated pheochromocytoma
- midazolam: drug hypersensitivity, severe chronic obstructive pulmonary disease, myasthenia gravis, sleep apnoea syndrome requiring CPAP, Parkinson's disease, severe respiratory insufficiency or acute respiratory depression
- Interactions with strong to moderate CYP inhibitors and inducers of the following P450 enzymes: CYP1A2 (inhibitors: ciprofloxacin, fluvoxamine), CYP2C9, CYP2C19, CYP2D6 (inhibitors: bupropion, cinacalcet, fluoxetine, quinidine, paroxetine, terbinafine) and CYP3A (inducers: apalutamide, carbamazepine, efavirenz, enzalutamide, phenobarbital, phenytoin, hypericum, lumacaftor, mitotane, nevirapine, primidone, rifabutin, rifampicin; inhibitors: clarithromycin, cobicistat, erythromycin, itraconazole, ketoconazole, posaconazole, ritonavir, voriconazole)41,42
- Use of concomitant medication with a clinically relevant PK or PD interaction with one or more components of the probe drug cocktail, if the interaction is expected to affect PK endpoint interpretation or compromise participant safety and cannot be appropriately managed
- Refusing or unable to give informed consent (e.g. hepatic encephalopathy)
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
The goal of this clinical trial is to learn how liver cirrhosis affects the way the body processes drugs in adults with different stages of liver cirrhosis. This information may help improve drug dosing for people with liver cirrhosis in the future. The main question it aims to answer is:
- How does the severity of liver cirrhosis affect the way the body processes a combination of five drugs, each used to measure the activity of a different liver enzyme?
Read more
Researchers will compare participants with mild, moderate, and severe liver cirrhosis to see whether the processing of drugs differs between these groups.
Participants will:
- Fast overnight for 8 hours before receiving the drugs
- Have a scan to measure the stiffness of their liver and spleen
- Receive a single low dose of five drugs: caffeine, warfarin, esomeprazole, metoprolol, and midazolam
- Have blood samples taken before and at several times up to 72 hours after receiving the drugs, including samples for genetic testing and blood clotting checks
- Avoid caffeine-containing food and drinks from 48 hours before receiving the drugs until the final blood sample
Read the detailed description
Objective: to identify and quantify the effect of changes in liver-metabolism that occur in different grades of cirrhosis disease severity on the PK of five probe drugs that are each selectively metabolised by one CYP isoform using a probe drug cocktail as proxy.
Study design: Single-dose interventional PK study
Study population: 45 patients with (decompensated) cirrhosis, 18 years or older.
Intervention: This study consists of a single intervention where patients receive a single oral administration of a drug probe cocktail. The oral probe drug cocktail consists of 100 mg caffeine, 5 mg warfarin, 20 mg esomeprazole, 50 mg metoprolol and 0.03 mg/kg midazolam.
Main study parameters/endpoints: The primary endpoint is the unbound clearance (CL) of each parent of the probe drugs with the total and unbound area under the plasma concentration versus time curve (AUC) of each drug. Secondary endpoints include pharmacokinetic (PK) parameters such as volume of distribution of the central (V1) and peripheral compartment (V2) and intercompartment clearance (Q) of each probe drug.
Secondary study parameters are:
- To identify covariates that may influence PK changes in cirrhosis in the development of a population PK model:
- Effect of different disease severity scores on PK (Model for End-stage Liver Disease (MELD) MELD, MELD-Na, MELD 3.0, reMELD-Na).
- Effect of presence of portal hypertension (ascites, hepatic encefalopathie (HE), spontaneous bacterial peritonitis (SBP), variceal bleeding)
- Effect of severity of portal hypertension on PK (spleen stiffness measurement; spleen stiffness measurement (SSM))
- Effect of inflammation on PK
- Effect of acute-on-chronic liver failure (ACLF) on PK
- Effect of concurrent acute kidney injury (AKI) on PK
- Effect of plasma albumin and bilirubin on PK
- Effect of CYP-polymorphisms on PK (metaboliser status and/or activity score of each CYP enzyme)
- Conditions
- Liver Cirrhosis
- Being tested
- Five-Drug CYP Probe Cocktail
- Keywords
- Pharmacokinetics, Drug metabolism, Cytochrome P450, Probe-drug cocktail, Cirrhosis, Hepatic impairment, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A, Precision dosing
- Medical subject headings
- Liver Cirrhosis, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Five-Drug CYP Probe CocktailDrug
Also called Caffeine, Warfarin, Esomeprazole, Metoprolol
A single dose of a five-drug CYP probe cocktail consisting of caffeine 100 mg, warfarin 5 mg, esomeprazole 20 mg, metoprolol 50 mg, and midazolam 0.03 mg/kg.
| Study group | Role | What they receive |
|---|---|---|
| Single-Dose Five-Drug CYP Probe Cocktail | Other | Participants with Child-Pugh class A, B, or C liver cirrhosis will receive the same single-dose combination of five CYP probe medicines. Pharmacokinetic outcomes will be compared between the three Child-Pugh classes. Receives: Drug: Five-Drug CYP Probe Cocktail |
What is being measured
The primary outcome is the main question the study is designed to answer.
Unbound clearance (CL) of each parent drug
Unbound clearance (CL) of each parent drug
Measured: 24 months
Total and unbound area under the plasma concentration versus time curve (AUC) of each parent drug
Total and unbound area under the plasma concentration versus time curve (AUC) of each parent drug
Measured: 24 months
Secondary outcomes (3)
Volume of distribution of the central compartment (V1) of each parent drug
Volume of distribution of the central compartment (V1) of each parent drug
Measured: 24 months
Volume of distribution of the peripheral compartment (V2) of each parent drug
Volume of distribution of the peripheral compartment (V2) of each parent drug
Measured: 24 months
Intercompartment clearance (Q) of each parent drug
Intercompartment clearance (Q) of each parent drug
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2026
- Study start1 Nov 2026 (estimated)
- Primary completion1 Nov 2028 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosisStudies 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 N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marten A Lantinga, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07750587
- Sponsor's protocol ID
- NL-011165
- Other IDs
- NL-OMON61340
- Acronym
- PRECISE
- Status last verified
- Aug 2026
- First submitted
- 3 Aug 2026
- Last updated
- 11 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Individual participant data is available upon reasonable request
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predicting Response and Exposure Changes in Cirrhosis for Effectiveness
- ClinicalTrials.gov ID
- NCT07750587
- Acronym / sponsor ID
- PRECISE / NL-011165
- Conditions
- Liver Cirrhosis
- Keywords
- Pharmacokinetics, Drug metabolism, Cytochrome P450, Probe-drug cocktail, Cirrhosis, Hepatic impairment, CYP1A2, CYP2C9
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- 1 Nov 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 6 Aug 2026 (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 goal of this clinical trial is to learn how liver cirrhosis affects the way the body processes drugs in adults with different stages of liver cirrhosis. This information may help improve drug dosing for people with liver cirrhosis in the future. The main question it aims to answer is:
- How does the severity of liver cirrhosis affect the way the body processes a combination of five drugs, each used to measure the activity of a different liver enzyme?
Researchers will compare participants with mild, moderate, and severe liver cirrhosis to see whether the processing of drugs differs between these groups.
Participants will:
- Fast overnight for 8 hours before receiving the drugs
- Have a scan to measure the stiffness of their liver and spleen
- Receive a single low dose of five drugs: caffeine, warfarin, esomeprazole, metoprolol, and midazolam
- Have blood samples taken before and at several times up to 72 hours after receiving the drugs, including samples for genetic testing and blood clotting checks
- Avoid caffeine-containing food and drinks from 48 hours before receiving the drugs until the final blood sample
Detailed description
Objective: to identify and quantify the effect of changes in liver-metabolism that occur in different grades of cirrhosis disease severity on the PK of five probe drugs that are each selectively metabolised by one CYP isoform using a probe drug cocktail as proxy.
Study design: Single-dose interventional PK study
Study population: 45 patients with (decompensated) cirrhosis, 18 years or older.
Intervention: This study consists of a single intervention where patients receive a single oral administration of a drug probe cocktail. The oral probe drug cocktail consists of 100 mg caffeine, 5 mg warfarin, 20 mg esomeprazole, 50 mg metoprolol and 0.03 mg/kg midazolam.
Main study parameters/endpoints: The primary endpoint is the unbound clearance (CL) of each parent of the probe drugs with the total and unbound area under the plasma concentration versus time curve (AUC) of each drug. Secondary endpoints include pharmacokinetic (PK) parameters such as volume of distribution of the central (V1) and peripheral compartment (V2) and intercompartment clearance (Q) of each probe drug.
Secondary study parameters are:
- To identify covariates that may influence PK changes in cirrhosis in the development of a population PK model:
- Effect of different disease severity scores on PK (Model for End-stage Liver Disease (MELD) MELD, MELD-Na, MELD 3.0, reMELD-Na).
- Effect of presence of portal hypertension (ascites, hepatic encefalopathie (HE), spontaneous bacterial peritonitis (SBP), variceal bleeding)
- Effect of severity of portal hypertension on PK (spleen stiffness measurement; spleen stiffness measurement (SSM))
- Effect of inflammation on PK
- Effect of acute-on-chronic liver failure (ACLF) on PK
- Effect of concurrent acute kidney injury (AKI) on PK
- Effect of plasma albumin and bilirubin on PK
- Effect of CYP-polymorphisms on PK (metaboliser status and/or activity score of each CYP enzyme)
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single-Dose Five-Drug CYP Probe Cocktail | Other | Drug: Five-Drug CYP Probe CocktailParticipants with Child-Pugh class A, B, or C liver cirrhosis will receive the same single-dose combination of five CYP probe medicines. Pharmacokinetic outcomes will be compared between the three Child-Pugh classes. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥ 18 years
- Clinical, radiological and/or histological diagnosis of cirrhosis
- Informed consent signed prior to participation in the study
Key exclusion criteria (19 listed)
- Original MELD score > 30
- Estimated creatinine clearance < 30 mL/min, calculated by using the Cockcroft-Gault equation
- Known poor metaboliser status for one of the CYP enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A) described in the medical record
- Previous clinically relevant adverse reaction or intolerance to one of the drugs in the probe drug cocktail
- Recent exposure to one of the drugs in the drug probe cocktail within five elimination half-lives prior to drug administration (corresponding to approximately 1-10 days depending on the probe drug)36-40:
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 |
|---|---|---|
| Five-Drug CYP Probe CocktailAlso: Caffeine, Warfarin, Esomeprazole, MetoprololA single dose of a five-drug CYP probe cocktail consisting of caffeine 100 mg, warfarin 5 mg, esomeprazole 20 mg, metoprolol 50 mg, and midazolam 0.03 mg/kg. | Drug | Single-Dose Five-Drug CYP Probe Cocktail |
Primary outcome
Unbound clearance (CL) of each parent drug
Time frame: 24 months
Unbound clearance (CL) of each parent drug
Total and unbound area under the plasma concentration versus time curve (AUC) of each parent drug
Time frame: 24 months
Total and unbound area under the plasma concentration versus time curve (AUC) of each parent drug
3 secondary outcomes
Volume of distribution of the central compartment (V1) of each parent drug
Time frame: 24 months
Volume of distribution of the peripheral compartment (V2) of each parent drug
Time frame: 24 months
Intercompartment clearance (Q) of each parent drug
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- Individual participant dataSharing planned: Undecided. Individual participant data is available upon reasonable request
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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.
Questions about this trial
What is this clinical trial studying?
A study testing Five-Drug CYP Probe Cocktail in people with Liver Cirrhosis, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
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 3 inclusion and 19 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: opening soon, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marten A Lantinga, MD PhD ((+31) (0)20 444 4444, m.a.lantinga@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Unbound clearance (CL) of each parent drug (time frame: 24 months). 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 11 Aug 2026.