Clinical trial NCT06380335: Study in Patients With Decompensated Liver Cirrhosis
Official title: A Multicentre, Observational Study in Patients With Liver Cirrhosis Who Have Hepatic Decompensation (OPAL)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Liver Cirrhosis
Keywords: Liver cirrhosis
Cirrhotic
Hepatic Cirrhosis
Chronic Liver Disease
Liver Fibrosis
Decompensated liver cirrhosis
Child-Pugh Score
MELD score
Liver function tests
Hepatic encephalopathy
End Stage Liver Disease (ESLD)
Retractable ascites
Variceal Bleeding
Lead sponsor: Resolution Therapeutics Limited
Sponsor class: NETWORK
First posted: 2024-04-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 1. Patients with liver cirrhosis who have been hospitalized for hepatic decompensation.
2. Out-patients with refractory ascites that does not require in-patient admission.

Brief summary: OPAL is a multicenter observational study, following the natural disease trajectory of participants who have permanent damage to their liver caused by scarring, sometimes also referred to as liver cirrhosis. These participants will also have recently had an acute worsening of their liver disease, which is also known as a hepatic decompensating event, which has resulted in them being admitted to hospital or required them to seek medical attention as an outpatient.

Detailed description: This multicenter, observational natural history study is designed to follow the disease trajectory of adults with cirrhosis of the liver who have a qualifying hepatic decompensation event.

The primary objective of the study is to obtain real world data to understand the clinical course of cirrhotic patients following a decompensation event in order to generate data to provide context for the safety and efficacy evaluation of future interventional treatments. Observed data will be collected from the visits and assessments conducted as part of the routine standard of care (SOC) follow-up of these patients. In addition, given the variability in SOC and timing of follow-up visits across institutions, if study required assessments do not coincide with a routine SOC visit at the institution, blood draws and other study-specific assessments will be collected at defined time points for the study analysis.

All participants who meet the eligibility criteria and stabilize following a hepatic decompensation event will have their clinical course followed for up to 96 weeks.

Eligibility criteria: Individuals eligible to participate in this study must meet the following criteria:

Inclusion Criteria:

1. Male or female age ≥18-75 years.
2. Patient is willing and able to provide informed consent to participate in the study.
3. Patient confirms willingness/ability to comply with all study procedures.
4. Has a diagnosis of liver cirrhosis determined by a physician based on at least one of the following:

   1. clinical and radiological features that correlate with a diagnosis of cirrhosis;
   2. transient elastography (TE) (FibroscanTM) \>15kPa;
   3. previous liver biopsy confirming histological features of cirrhosis.
5. 5. For eligibility at Screen Part 2 - Aetiology of liver disease of steatotic liver disease (SLD) including pure metabolic dysfunction associated steatotic liver disease (MASLD) or metabolic and alcohol related/associated liver disease (Met-ALD), or alcohol-related liver diseases (ALD).

   a. Patients with ALD or Met-ALD only if they are confirmed to not be drinking alcohol above Met-ALD limits defined in this protocol AND have phosphatidyl ethanol (PEth) test \<200 ng/ml. (N.B. No more than 34% of the total patients in this protocol will be ALD \[excludes Met-ALD\]).
6. Meets one of the following criteria:

   1. a. Hospitalised as an in-patient for a recent major hepatic decompensation event (qualifying event) including ascites, HE or variceal bleed, HRS-AKI or SBP, this being the only hospitalisation for an hepatic decompensation event within the last 6 months, and where recent is defined as within 6 weeks of hospital discharge OR
   2. Out-patient: Medically refractory ascites is defined by the repeated (≥ 2) need for LVP (i.e., therapeutic, not diagnostic) at least once per 8 weeks despite best medical attempts to control the ascites by sodium restriction and diuretic treatment, as confirmed by the Investigator, with date on of onset \[defined as the date of the second therapeutic paracentesis\] occurring within the past 6 months.
7. MELD 3.0 score of 12-20 taken within 2 weeks of qualifying event.
8. Has stabilised post-hepatic decompensation event, as defined by two MELD assessments (within 1 point of each) other taken within 2 weeks, or physician assessed as stable. with the ability to safely cell mobilise with GCSF, apherese and received RTX001 treat in the interventional Phase 1/2 study.

Exclusion Criteria:

1. Liver cirrhosis due to:

   1. any viral hepatitis , or
   2. autoimmune and cholestatic aetiologies including, but not limited to, primary biliary cholangitis and primary sclerosing cholangitis.
2. Acute liver disease in the absence of underlying liver cirrhosis, including, but not limited to, drug induced liver injury.
3. Any current organ failure requiring more than out-patient non-invasive supportive care, and not associated with the patient's qualifying hepatic decompensation event.
4. Known splenomegaly ≥16cm.
5. Thrombocytopenia \<50,000 mm3.
6. Sepsis (with positive microbial cultures) or as defined by the Investigator, unless stable and is at least 4 weeks after having completed a full course of intravenous antibiotics.
7. Presence or suspicion of any of the following co-morbidities:

   1. a. history of liver transplantation or other organ transplant;
   2. ACLF;
   3. known human immunodeficiency virus;
   4. pulmonary embolism;
   5. hepatocellular carcinoma, or active malignant disease within the last 5 years, (excluding non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, benign polyps etc.);
   6. co-hepatic morbidities e.g., portal vein thrombosis;
   7. hepatic hydrothorax unless it is a small hydrothorax, not clinically apparent, that is detected incidentally by radiologic evaluation that does not require clinical intervention.
   8. chronic renal impairment (on dialysis) or unresolved acute kidney injury;
   9. acute or chronic heart failure (New York Heart Association Grade III/IV);
   10. porto-pulmonary hypertension;
   11. severe chronic lung disease e.g., chronic obstructive pulmonary disease or interstitial lung disease where the forced expiratory volume (FEV1) is less than 50% and/or FEV1/forced vital capacity is less than 60%;
   12. hepatopulmonary syndrome;
   13. history or current treatment with chronic albumin treatment;
   14. significant untreated/unstable psychiatric disease;
   15. transjugular intrahepatic portosystemic shunt (TIPSS) within the previous 6 months.
8. Current or planned use of immunosuppressive medication, with the exception of low doses up to 10 mg/day prednisone or equivalent, or inhaled steroids to manage an asthma, which are permitted.
9. Any other intercurrent illness that is either life-threatening or of clinical significance such that it might limit compliance with study procedures, in the Investigator's opinion.
10. Current alcohol misuse defined as alcohol intake greater than 3 units/day for females and 4 units/day for males, or binge drinking (\>14 units/day) as determined by the Investigator or PEth alcohol test \>200 ng/ml. One alcohol unit is equivalent to14 g of alcohol: a half-pint (\~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. Note: patients with history of exceeding these alcohol use limits, if meeting all other inclusion/exclusion criteria, are limited to 34% of enrolled patients.
11. Intake of non-medically supervised drugs of abuse that is judged (by the Investigator) to be a high risk to the patient's acute health or which makes the patient likely to be non-compliant with follow-up.
12. Are currently participating in an investigational interventional study. Note: concurrent participation in another non-interventional study is permitted.

Primary outcomes:
measure: Examine the characteristics of patients admitted to hospital with hepatic decompensation.
timeFrame: Baseline and up to 96 weeks
measure: Examine the characteristics of patients admitted to hospital with hepatic decompensation.
timeFrame: Baseline and up to 96 weeks
measure: Examine the characteristics of patients admitted to hospital with hepatic decompensation.
timeFrame: Baseline and up to 96 weeks
measure: Examine the characteristics of patients admitted to hospital with hepatic decompensation.
timeFrame: Baseline, and up to 96 weeks
measure: Examine the characteristics of patients admitted to hospital with hepatic decompensation.
timeFrame: Baseline, and up to 96 weeks
measure: Examine the characteristics of patients admitted to hospital with hepatic decompensation.
timeFrame: Baseline, and up to 96 weeks
Secondary outcomes:
measure: Follow the natural history of patients admitted to hospital with hepatic decompensation.
timeFrame: Screening up to 96 weeks
measure: Follow the natural history of patients admitted to hospital with hepatic decompensation.
timeFrame: Screening up to 96 weeks
measure: Follow the natural history of patients admitted to hospital with hepatic decompensation.
timeFrame: Screening up to 96 weeks
measure: Follow the natural history of patients admitted to hospital with hepatic decompensation.
timeFrame: Screening up to 96 weeks
measure: Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.
timeFrame: Screening up to 96 weeks
measure: Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.
timeFrame: Screening up to 96 weeks
measure: Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.
timeFrame: Screening up to 96 weeks
measure: Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.
timeFrame: Screening up to 96 weeks
measure: Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.
timeFrame: Screening up to 96 weeks
measure: Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.
timeFrame: Screening up to 96 weeks
measure: Examine the characteristics and natural history of patients with medically refractory ascites that do not require hospitalisation.
timeFrame: Screening up to 96 weeks
Other outcomes:
measure: Explore clinical and laboratory parameters.
timeFrame: Screening up to 96 weeks
measure: Evaluate the effect of disease progression on biomarkers of inflammatory activity
timeFrame: Screening up to 96 weeks
Locations:
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary Edinburgh
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospital NHS Trust
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: London
country: United Kingdom
facility: St Mary's Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
Study officials:
References: