Diese Seite wurde automatisch übersetzt und die Genauigkeit der Übersetzung wird nicht garantiert. Bitte wende dich an die englische Version für einen Quelltext.

Leberzirrhose-Netzwerk Rosuvastatin Wirksamkeit und Sicherheit für Zirrhose in den Vereinigten Staaten (LCN RESCU)

23. September 2026 aktualisiert von: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Liver Cirrhosis Network (LCN) Rosuvastatin Efficacy and Safety for Cirrhosis in the United States (RESCU): Eine doppelblinde, randomisierte, Placebo-kontrollierte Phase-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.

Studienübersicht

Status

Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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).

Studientyp

Interventionell

Einschreibung (Geschätzt)

260

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studieren Sie die Kontaktsicherung

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre bis 75 Jahre (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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)

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Vervierfachen

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 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.
Arzneimittel: 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.

Andere Namen:
  • 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.
Arzneimittel: 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.

Andere Namen:
  • Rosuvastatin 20 mg

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Mean change in liver stiffness
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Time to disease progression
Zeitfenster: 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
Zeitfenster: 96 weeks

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

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

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

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

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

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

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

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

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

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

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

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

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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

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

Mitarbeiter

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

Ermittler

  • Hauptermittler: Abigail Smith, PhD, Northwestern University

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Nützliche Links

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

7. Dezember 2023

Primärer Abschluss (Geschätzt)

31. August 2029

Studienabschluss (Geschätzt)

31. August 2029

Studienanmeldedaten

Zuerst eingereicht

24. März 2023

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

14. April 2023

Zuerst gepostet (Tatsächlich)

27. April 2023

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

28. September 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

23. September 2026

Zuletzt verifiziert

1. September 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • Pro00070580
  • 5U24DK130164-04 (US NIH Stipendium/Vertrag)

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

JA

Beschreibung des IPD-Plans

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

Art der unterstützenden IPD-Freigabeinformationen

  • STUDIENPROTOKOLL
  • ICF

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Ja

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

Abonnieren