Decompensated Liver Cirrhosis
Conditions
Brief summary
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 .
Detailed description
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.
Interventions
DRUGDarbepoetin
Darbepoetin will be given s/c at dose of 40 mcg once a week (total 4 doses) for 1 month
DRUGG-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
DRUGLactulose
Standard Medical Tretament part
BIOLOGICALAlbumin
Standard Medical Tretament part
Sponsors
Institute of Liver and Biliary Sciences, India
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-70 years 2. Decompensated cirrhosis patients 3. Uncomplicated ascites, 4. CTP ≤ 9B and MELD \<16 5. BM Hematopoietic stem cell reserve \> 0.4 6. Given informed consent
Exclusion criteria
1. Patients with age less than 18 years or more than 65 years 2. Lack of informed consent 3. Patients with a history of serious allergic reactions to the active component, filgrastim, other human granulocyte colony-stimulating factors, or any of the ingredients 4. Evidence of alcoholic hepatitis/active alcohol abuse last intake ≤ 3 months 5. Suspected autoimmune hepatitis (ANA/ASMA-positive in titers 1:80 and/ or IgG 1.5 times upper limit of normal), 6. Hemolytic anaemia -Sickle cell disease or thalassemia 7. Patients with Grade III ascites /complicated ascites 8. Patients with large spleen (size ≥ 15cm) 9. Recent variceal bleeding in less than 42 days 10. Patients with any focus of sepsis as proven by culture positivity or presence of spontaneous Bacterial Peritonitis (SBP) 11. H/o Seizures 12. Hepatocellular Carcinoma (HCC) or other malignancy 13. Acute Kidney Injury (AKI) with serum Creatinine \>1.5 mg/ dl, 14. Multi-organ failure, 15. Hepatic Encephalopathy or prior history of HE in less than 6months 16. HIV seropositivity, 17. Uncontrolled essential hypertension, CAD /Stroke 18. Massive hydrothorax 19. Pregnancy 20. Viral etiology of liver disease 21. Chronic kidney disease 22. Portal vein thrombosis 23. Planned for LT 24. Bone marrow hematopoietic stem cells \< 0.4
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in innate immunity between the groups. | 6 months | Innate immunity -Monocyte, neutrophils -distribution , function and bioenergetic adaptation |
Secondary
| Measure | Time frame |
|---|---|
| Number of participants with change in adaptive immunity(T-cell, B-cell and NK cells distribution only ) | 6 months |
| Number of participants with change in inflammation (a panel of pro and anti-inflammatory cytokines). | 6 months |
| Change in gcsf levels and EPO levels at baseline and completion of each cycle. | 6 months |
| Proportion of participants completing treatment without major adverse effects; | 6 months |
| Number of participants with improvement in liver disease severity indices (MELD). | 6 months |
| Proportion of participants developed new-onset of LRE (such as ascites, HE, AKI, bleed and sepsis) or show mortality in all the groups. | 6 months |
| Cumulative incidence of second decompensation in all the groups. | 6 months & 1 year |
| Transplant-free survival. | 6 months & 1 year |
| Number of participants with improvement in liver disease severity indices (CTP). | 6 months |
| Number of participants with change in peripheral blood CD34+ Hematopoietic Stem Cells count at 6months. | 6 months |
Countries
India
Contacts
Primary ContactDr Shreya Singh, MD
Backup ContactDr Manoj Kumar Sharma, DM
Outcome results
None listed