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Levercirrhosis Network Rosuvastatin Effekt og sikkerhet for skrumplever i USA (LCN RESCU)

23. september 2026 oppdatert av: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Levercirrhosis Network (LCN) Rosuvastatin Effekt og sikkerhet for skrumplever i USA (RESCU): En dobbeltblind randomisert, placebokontrollert fase 2-studie

This is a double-blind, phase 2 study to evaluate safety and efficacy of rosuvastatin in comparison to placebo after 2 years in patients with compensated cirrhosis.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

This study is a randomized, double-blind, placebo-controlled Phase 2 clinical trial, of 20mg of rosuvastatin by mouth, once daily. Participants will be randomized (1:1) to either once daily placebo or once daily rosuvastatin.

Patients meeting all eligibility criteria will be assigned to a randomization arm prior to initiation of a 4-week lead-in phase of the study. All participants will undergo a 4-week, open-label active run-in phase to evaluate initial safety and adherence to rosuvastatin. During this active run-phase, all participants will receive target dose rosuvastatin-- 20 mg daily. After the active run-in phase, all participants will continue with their pre-assigned randomization (1:1) treatment of rosuvastatin 20 mg daily or matching placebo.

The total duration of the study will be 96 weeks in the assigned treatment arm plus the 4-week lead-in period. The primary outcome will be the mean change in liver stiffness from the baseline measurement to the end of study liver stiffness, as measured by ultrasound-based vibration-controlled transient elastography (VCTE).

There are 10 participating clinical centers, and we anticipate a total of 260 patients will be recruited for the initial lead-in as we estimate 20% of participants may dropout after the lead-in (260 x 0.8 = 208 for randomization into the study drug treatment phase).

Studietype

Intervensjonell

Registrering (Antatt)

260

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

  • Forente stater
    • California
      • La Jolla, California, Forente stater, 92035
        • Rekruttering
        • University of California San Diego NAFLD Research Center
        • Ta kontakt med:
      • Los Angeles, California, Forente stater, 90033
      • Los Angeles, California, Forente stater, 90033
      • San Francisco, California, Forente stater, 94143
      • San Francisco, California, Forente stater, 94110
        • Rekruttering
        • UCSF/Zuckerberg San Francisco General Hospital and Trauma Center
        • Ta kontakt med:
    • Florida
      • Miami, Florida, Forente stater, 33122
    • Michigan
      • Ann Arbor, Michigan, Forente stater, 48109
    • Minnesota
      • Rochester, Minnesota, Forente stater, 55901
    • New York
      • New York, New York, Forente stater, 10021
      • New York, New York, Forente stater, 10031
        • Rekruttering
        • Columbia University Iriving School of Medicine
        • Ta kontakt med:
    • North Carolina
      • Durham, North Carolina, Forente stater, 27710
    • Ohio
      • Cleveland, Ohio, Forente stater, 44192
        • Rekruttering
        • Cleveland Clinic
        • Ta kontakt med:
    • Virginia
      • Richmond, Virginia, Forente stater, 23298

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 75 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria

  1. Age 18-75 years

  2. Cirrhosis due to NAFLD, ALD, or chronic viral hepatitis (treated HBV or HCV)

  3. Clinical diagnosis of cirrhosis as defined by investigator confirmation and the following:

    a. At least one liver biopsy within 5 years prior to consent showing either: Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis, OR b. At least 2 of the following: i. Evidence on imaging: Nodular liver with either splenomegaly or recanalized umbilical vein within the past 48 weeks ii. Liver stiffness: VCTE within 48 weeks prior to consent or during Screening ≥15.0 kPa or MRE within 48 weeks prior to consent or during Screening ≥5 kPa iii. Evidence of varices demonstrated on imaging or endoscopy within 3 years prior to consent or during Screening iv. Either: FIB-4>2.67 or platelets <150/mL within 6 months prior to consent or during Screening

  4. Two measures of VCTE: one at screening and one at the open-label dispense study visit, meeting the following criteria:

    1. The first measure must be ≥ 15.0 kPa.
    2. The two measures must be at least 2 hours apart and no more than 60 days apart from one another.
    3. The mean of two measurements must be ≥ 15.0 kPa.
    4. Additionally, both screening and open-label dispense liver stiffness measures must be ≤50 kPa

  5. Compensated defined by:

    1. Absence of ascites/hydrothorax, hepatic encephalopathy or variceal bleeding currently or in the last 48 weeks, as determined clinically by investigator.
    2. If prior history of decompensation, must be without current symptoms of decompensation and no longer requiring treatment of complications for the last 48 weeks, including the use of diuretics for the treatment of ascites, and/or rifaximin or lactulose for the treatment of hepatic encephalopathy. Use of non-selective beta blockers will be allowed.
    3. Child-Pugh score <8

  6. Provision of written informed consent. Exclusion Criteria

  1. Currently on a statin or any statin exposure within 24 weeks prior to consent.

  2. Known indication for statin therapy, defined as:

    1. Prior peripheral vascular, cardiovascular or cerebrovascular event for which statins are indicated for secondary prevention, OR
    2. Documented familial hypercholesterolemia, heterozygous familial hypercholesterolemia, OR
    3. Fasting LDL-C ≥ 190 mg/dL

  3. Myocardial infarction, Unstable angina, transient ischemic events, or stroke within 24 weeks of screening.

  4. Alcohol Use Disorder Identification Test (AUDIT) total score of ≥8 at screening.

  5. Patients with limitations in attending study visits.

  6. Prisoners.

  7. Known prior or current hepatocellular carcinoma (HCC) or cholangiocarcinoma.

  8. Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrograde transvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of time of occurrence.

  9. Current (in past 24 weeks prior to consenting) use of medications known to cause hepatic fibrogenesis or confound endpoint assessment, defined as:

    1. amiodarone
    2. methotrexate
    3. warfarin

  10. Current (in past 24 weeks prior to consenting) use of medications which may increase risk for rosuvastatin-related myositis or DILI, defined as:

    1. fenofibrate

    2. erythromycin

    3. gemfibrozil

    4. niacin (500 mg or more)

    5. HIV protease inhibitors (darunivar, indinavir, nelfinavir, amprenavir)

    6. colchicine

    7. cyclosporin

    8. Additional medications that will be excluded:

      atazanavir/ritonavir capmatinib darolutamide dasabuvir/ombitasvir/paritaprevir/ritonavir ledipasvir/sofosbuvir elbasvir/grazoprevir erythromycin lopinavir/ritonavir regorafenib ritonavir, in any combination simeprevir sofbuvir/velpatasvir/voxilaprevir sofosbuvir/velpatasvir tafamidis tamoxifen teriflunomide

      *If exposure was for 7 or less days for one of these medications can consider enrollment after 28 days from final dose.

  11. Presence of portal or hepatic vein thrombosis

  12. Diagnosis of untreated hypothyroidism or on unstable treatment regimen for hypothyroidism

  13. Receiving an elemental diet or parenteral nutrition

  14. Chronic pancreatitis or pancreatic insufficiency

  15. Etiology of cirrhosis other than ALD, NAFLD, or viral hepatitis (excluded diagnoses include cryptogenic immune-mediated such as AIH, PSC and PBC, cardiac cirrhosis or Fontan-associated liver disease, A1AT, Wilson's disease, etc.)

  16. Conditions which may confound study outcome:

    a. Unstable or active inflammatory bowel disease b. Active infection c. Any malignant disease (other than squamous or basal cell carcinoma of the skin) within previous 3 years d. Prior solid organ or hematopoietic cell transplant e. Bariatric surgery in the last 24 weeks prior to consent or planned bariatric surgery within the next 96 weeks f. Current liver-unrelated end-stage organ failures such as end-stage renal disease on dialysis, stage 3-4 congestive heart failure (CHF), current chronic obstructive pulmonary disease (COPD) on home oxygen.

  17. Known current medical or psychiatric conditions which, in the opinion of the investigator, would make the participant unsuitable for the study for safety reasons or interfere with or prevent adherence to the protocol.

  18. The following laboratory abnormalities within 90 days of screening:

    a. Hemoglobin <10 g/dL b. Albumin <3.0 g/dL c. Prolonged international normalized ratio (INR) >1.5 d. Total bilirubin ≥ 2.0 mg/dl (unless due to Gilbert's syndrome or hemolysis as denoted by normal direct bilirubin fraction) e. Direct bilirubin ≥ 0.9 f. Uncontrolled diabetes (HbA1c ≥ 9.5%) within past 90 days.

  19. Kidney function abnormalities including:

    1. Dialysis
    2. Baseline eGFR < 30 cc/min with CKD-Epi equation
    3. Known nephrotic proteinuria, defined as 3g or greater of protein in 24-hour urine collection

  20. Recent (within 48 weeks) or present hepatic decompensation with ascites/hydrothorax, hepatic encephalopathy or variceal bleeding

  21. Untreated chronic hepatitis B or C infection

    1. HCV eligible for enrollment if HCV RNA negative at baseline or documentation of prior SVR12
    2. HBV eligible if an HBV DNA <100 IU/mL within the last 48 weeks and on treatment

  22. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 200 U/L within the past 24 weeks or alkaline phosphatase (ALP) ≥ 300.

  23. Documented history of intolerance to statins

  24. Serious comorbid medical disease which in the investigator's opinion renders a life-expectancy less than 96 weeks

  25. Active illicit substance use (other than THC), including inhaled or injected drugs, in the 24 weeks prior to screening

  26. Pregnancy, planned pregnancy or breastfeeding

  27. Current participation in active medication treatment trials (within 24 weeks prior to randomization) or planned participation in active medication treatment trials simultaneous to participation in present trial.

  28. Significant existing muscle pain or tenderness or prior history of myasthenia gravis as determined by a site physician.

  29. Failure or inability to provide informed consent.

  30. East Asian Descent within one degree of relatedness (e.g., if the participant's parents are of East Asian descent)

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Active

Open-label lead-in period of 4 weeks on 20 mg rosuvastatin by mouth once daily, followed by a period of 96 weeks rosuvastatin 20 mg daily.
Legemiddel: Rosuvastatin

Patients meeting all eligibility criteria will be assigned to a randomization arm prior to initiation of a 4-week lead-in phase of the study. All participants will undergo a 4-week, open-label active run-in phase to evaluate initial safety and adherence to rosuvastatin. During this active run-phase, all participants will receive target dose rosuvastatin-- 20 mg daily . After the active run-in phase, all participants will continue with their pre-assigned randomization (1:1) treatment of rosuvastatin 20 mg daily or matching placebo.

Andre navn:
  • Rosuvastatin 20 mg
Placebo komparator: Placebo

Open-label lead-in period of 4 weeks on 20 mg rosuvastatin by mouth once daily, followed by a period of 96 weeks placebo.
Legemiddel: Rosuvastatin

Patients meeting all eligibility criteria will be assigned to a randomization arm prior to initiation of a 4-week lead-in phase of the study. All participants will undergo a 4-week, open-label active run-in phase to evaluate initial safety and adherence to rosuvastatin. During this active run-phase, all participants will receive target dose rosuvastatin-- 20 mg daily . After the active run-in phase, all participants will continue with their pre-assigned randomization (1:1) treatment of rosuvastatin 20 mg daily or matching placebo.

Andre navn:
  • Rosuvastatin 20 mg

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Mean change in liver stiffness
Tidsramme: 96 weeks

Mean change in liver stiffness as measured in kilopascal with Vibration-Controlled Transient Elastography between study entry and week 96. Range: 2 to 75 kilopascal. Higher stiffness indicates increased disease progression
96 weeks

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Time to disease progression
Tidsramme: 96 weeks

Time to disease progression defined as time to development of decompensation event (ascites, hepatic encephalopathy, variceal bleed) or hepatocellular carcinoma. Analyzed as time-to-event; binary if low counts.
96 weeks
All-cause mortality
Tidsramme: 96 weeks

All-cause mortality: time-to-event, binary if low counts
96 weeks
Time to development of ascites
Tidsramme: 96 weeks

Ascites: time-to-event, binary if low counts
96 weeks
Time to development of overt hepatic encephalopathy
Tidsramme: 96 weeks

Time to development of overt hepatic encephalopathy: time-to-event, binary if low counts
96 weeks
Time to development of variceal bleed
Tidsramme: 96 weeks

Variceal bleed: time-to-event, binary if low counts
96 weeks
Time to development of hepatocellular carcinoma
Tidsramme: 96 weeks

Hepatocellular carcinoma: time-to-event, binary if low counts
96 weeks
Change in spleen stiffness as measured by Vibration-Controlled Transient Elastography (VCTE)
Tidsramme: 96 weeks

Units: kilopascal; Range: 5 to 100 kilopascal; higher stiffness indicates increased disease progression
96 weeks
Change in Child-Turcotte-Pugh score
Tidsramme: 96 weeks

Ordinal score from 5 to 15; higher score indicates further disease progression
96 weeks
Change in Model for End Stage Liver Disease - Sodium (MELD-Na)
Tidsramme: 96 weeks

Unitless; Range: 6-40; higher score indicates further disease progression
96 weeks
Change in liver stiffness via Magnetic Resonance Elastography
Tidsramme: 96 weeks

Units: kilopascal; Range: 0 to 20; higher stiffness indicates increased disease progression
96 weeks
Change in Enhanced Liver Fibrosis test
Tidsramme: 96 weeks

Unitless; Range: 5 to 11; Higher score is worse
96 weeks
Change in Fibrosis-4
Tidsramme: 96 weeks

Unitless; Range: 0 to 10; higher score indicates more stiffness
96 weeks
Change in patient-reported quality of life scores
Tidsramme: 96 weeks

Patient Reported Outcomes Measurement Information System (29-item version) Global Health T-Score: Population centered at 50 points, standard deviation of 10 (higher score signifies "better" health)
96 weeks
Rate of adverse events
Tidsramme: 96 weeks

Count
96 weeks
Rate of serious adverse events
Tidsramme: 96 weeks

Count
96 weeks
Rate of adverse events of special interest
Tidsramme: 96 weeks

Rate of adverse events of special interest (myopathy, drug-induced liver injury, cardiovascular events, cancer other than hepatocellular carcinoma, new onset diabetes as separate outcomes): Count
96 weeks
Time to cardiovascular events
Tidsramme: 96 weeks

Cardiovascular events: time-to-event, binary if low counts
96 weeks
Time to new onset diabetes
Tidsramme: 96 weeks

New onset diabetes: time-to-event, binary if low counts
96 weeks

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Samarbeidspartnere

National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Cancer Institute (NCI)
Mayo Clinic
University of California, San Diego
University of Miami
Columbia University
University of Michigan
The Cleveland Clinic
Duke University
University of Southern California
Weill Medical College of Cornell University
University of California, San Francisco
Virginia Commonwealth University
LAC+USC Medical Center

Etterforskere

  • Hovedetterforsker: Abigail Smith, PhD, Northwestern University

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

7. desember 2023

Primær fullføring (Antatt)

31. august 2029

Studiet fullført (Antatt)

31. august 2029

Datoer for studieregistrering

Først innsendt

24. mars 2023

Først innsendt som oppfylte QC-kriteriene

14. april 2023

Først lagt ut (Faktiske)

27. april 2023

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

28. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

23. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • Pro00070580
  • 5U24DK130164-04 (U.S. NIH-stipend/kontrakt)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

Dataset with National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Repository.

IPD-deling Støtteinformasjonstype

  • STUDY_PROTOCOL
  • ICF

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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