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.

Institute of Liver and Biliary Sciences, India

Status: Not yet enrolling

Conditions: Decompensated Liver Cirrhosis

Treatments: Drug: Darbepoetin; Drug: G-CSF; Biological: Albumin; Drug: Lactulose

Study type: Interventional

Funder types: Other

Identifiers

NCT07002827

ILBS-Cirrhosis-73

Details and patient eligibility

About

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 .

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 3 patient groups

Standard Medical treatment

Active Comparator group

Description:

Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.

Treatment:

Drug: Lactulose

Biological: Albumin

Single cycle of G-CSF + darbepoetin and standard medical treatment

Experimental group

Description:

* 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. * Darbepoetin will be given s/c at dose of 40 mcg once a week (total 4 doses) for 1 month. * Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.

Treatment:

Drug: Lactulose

Biological: Albumin

Drug: G-CSF

Drug: Darbepoetin

Three cycles of G-CSF + darbepoetin and standard medical treatment (1-month, 3-month, and 5-month)

Experimental group

Description:

* 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. * Darbepoetin will be given s/c at dose of 40 mcg once a week (total 4 doses) for 1 month. * Standard medical therapy including lactulose, bowel enema and albumin will be continued in both groups.

Treatment:

Drug: Lactulose

Biological: Albumin

Drug: G-CSF

Drug: Darbepoetin