Effect of Single vs Repeated Cycles of a Combination of Granulocyte Colony Stimulating Factor and Darbepoetin vs Standard Medical Treatment on Immunometabolic Profile in Patient With Early Decompensated Cirrhosis.

Официальное название

Effect of Single vs Repeated Cycles of a Combination of Granulocyte Colony Stimulating Factor and Darbepoetin vs Standard Medical Treatment on Immunometabolic Profile in Patient With Early Decompensated Cirrhosis -A Pilot Randomised Controlled Trial.

Обзор

Exogenous growth factor-mobilized bone marrow (BM) stem cells(G-CSF) and DARBEPOETIN use have shown a differential response in the management of decompensated cirrhosis (DC) with improved survival, CTP and MELD scores. This study was designed to evaluate potential clinical benefit of repeated cycles of granulocyte-colony stimulating factor (G-CSF) and DARBEPOETIN versus single cycle on delta change in immunometabolic profile of patients at 6 months assessed in terms of -Change in innate immunity -Monocyte, neutrophils -distribution , function and bioenergetic adaptation .

Подробное описание

Aim: To study the efficacy of single vs repeated cycle of Granulocyte Colony Stimulating Factor+ darbopoetin vs standard medical treatmenton immunometabolic profile in patient with early decompensated cirrhosis

Study population:

* Age 18-70 years * Early decompensated cirrhosis MELD \< 16 , CTP \< 9B * Uncomplicated ascites * A Prospective Randomized Controlled Trial. * Single Centre. * Open label. * Block Randomization will be done , it will be implemented by IWRS method. * The study will be conducted in Department of Hepatology, ILBS.

Вмешательства

• Препарат Darbepoetin
  Darbepoetin will be given s/c at dose of 40 mcg once a week (total 4 doses) for 1 month
• Препарат G-CSF
  G-CSF will be given at a dose of 5 µg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30
• Препарат Lactulose
  Standard Medical Tretament part
• Биопрепарат Albumin
  Standard Medical Tretament part

Первичные конечные точки

• Change in innate immunity between the groups. [Срок оценки: 6 months]

Вторичные конечные точки (10)

• Proportion of participants developed new-onset of LRE (such as ascites, HE, AKI, bleed and sepsis) or show mortality in all the groups. [Срок оценки: 6 months]
• Cumulative incidence of second decompensation in all the groups. [Срок оценки: 6 months & 1 year]
• Transplant-free survival. [Срок оценки: 6 months & 1 year]
• Number of participants with improvement in liver disease severity indices (CTP). [Срок оценки: 6 months]
• Number of participants with improvement in liver disease severity indices (MELD). [Срок оценки: 6 months]
• Number of participants with change in adaptive immunity(T-cell, B-cell and NK cells distribution only ) [Срок оценки: 6 months]
• Number of participants with change in inflammation (a panel of pro and anti-inflammatory cytokines). [Срок оценки: 6 months]
• Change in gcsf levels and EPO levels at baseline and completion of each cycle. [Срок оценки: 6 months]
• Proportion of participants completing treatment without major adverse effects; [Срок оценки: 6 months]
• Number of participants with change in peripheral blood CD34+ Hematopoietic Stem Cells count at 6months. [Срок оценки: 6 months]

Критерии участия

Критерии включения

• Age 18-70 years
• Decompensated cirrhosis patients
• Uncomplicated ascites,
• CTP ≤ 9B and MELD <16
• BM Hematopoietic stem cell reserve > 0.4
• Given informed consent

Критерии исключения

• Patients with age less than 18 years or more than 65 years
• Lack of informed consent
• Patients with a history of serious allergic reactions to the active component, filgrastim, other human granulocyte colony-stimulating factors, or any of the ingredients
• Evidence of alcoholic hepatitis/active alcohol abuse last intake ≤ 3 months
• Suspected autoimmune hepatitis (ANA/ASMA-positive in titers 1:80 and/ or IgG 1.5 times upper limit of normal),
• Hemolytic anaemia -Sickle cell disease or thalassemia
• Patients with Grade III ascites /complicated ascites
• Patients with large spleen (size ≥ 15cm)
• Recent variceal bleeding in less than 42 days
• Patients with any focus of sepsis as proven by culture positivity or presence of spontaneous Bacterial Peritonitis (SBP)
• H/o Seizures
• Hepatocellular Carcinoma (HCC) or other malignancy
• Acute Kidney Injury (AKI) with serum Creatinine >1.5 mg/ dl,
• Multi-organ failure,
• Hepatic Encephalopathy or prior history of HE in less than 6months
• HIV seropositivity,
• Uncontrolled essential hypertension, CAD /Stroke
• Massive hydrothorax
• Pregnancy
• Viral etiology of liver disease
• Chronic kidney disease
• Portal vein thrombosis
• Planned for LT
• Bone marrow hematopoietic stem cells < 0.4

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Индия · 1 центр

• Institute of Liver & Biliary Sciences (ILBS) — New Delhi

Идентификаторы

NCT: NCT07002827 · ILBS-Cirrhosis-73

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗