NCT03911037

GCSF Therapy in Decompensated Cirrhosis - A Double Blinded RCT

Status unknown Phase 2, PHASE3 Last updated 19 July 2019

What this trial tests

Phase 2, PHASE3 trial testing G-CSF in Decompensated Cirrhosis of Liver in 70 participants. Status unknown.

Timeline

4 May 2019

Primary endpoint
30 June 2020

30 June 2020

Quick facts

Lead sponsor	Post Graduate Institute of Medical Education and Research, Chandigarh
Phase	Phase 2, PHASE3
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	70
Start date	4 May 2019
Primary completion	30 June 2020
Estimated completion	30 June 2020
Sites	1 location across India

Drugs / interventions tested

• G-CSF (g-csf) — full drug profile →
• Placebo

Conditions studied

• Decompensated Cirrhosis of Liver — all drugs for Decompensated Cirrhosis of Liver →

Sponsor

Post Graduate Institute of Medical Education and Research, Chandigarh

Who can join

Adults 18 to 80, any sex, with Decompensated Cirrhosis of Liver. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Cirrhosis of liver is a leading cause of morbidity and mortality worldwide. Complications like ascites, spontaneous bacterial peritonitis, variceal bleed, hepatic encephalopathy, hepatorenal syndrome (HRS) and hepatocellular carcinoma (HCC) portend a poor prognosis and further decreases survival in these patients. The major causes of cirrhosis include excessive alcohol consumption, viral hepatitis and non- alcoholic fatty liver disease.

Currently the only definitive treatment option for cirrhosis is liver transplantation which is limited in its applicability due to donor shortage, exorbitant costs and lack of widespread availability. Moreover, it requires lifelong immunosuppression and has considerable long term side effects including chronic renal failure, post-transplant lymphoproliferative disease and cardiovascular complications.

The ability of stem cells to differentiate into multiple cellular lineages makes one speculate that stem cells can be used for tissue repair and regeneration when tissue-resident stem cells become overwhelmed. It has been shown that in response to acute or chronic liver damage, bone marrow derived stem cells can spontaneously populate the liver and differentiate into hepatic cells, thereby contributing to hepatic regeneration. Thus, apart from hepatocytes and intrahepatic stem cells, bone marrow derived stem cells also participate in the liver regeneration process.

Currently, there are two methods to mobilize stem cells from the bone marrow to the liver. One is administration of cytokines like granulocyte-colony stimulating factor (G-CSF) and the other is the isolation of stem cells from the marrow and their injection into the hepatic artery or portal vein after purification. The latter is probably more cumbersome and may be potentially risky due to the underlying coagulation abnormalities in cirrhotic patients. Improved liver histology and survival has been noted in patients with cirrhosis following mobilization of bone marrow stem cells by granulocyte-colony stimulating factor (G-CSF).

Three recent studies have demonstrated G-CSF induced mobilization of bone marrow stem cells (CD34 cells) in peripheral blood and their subsequent increase in liver tissue and improved survival in patients with alcoholic hepatitis and ACLF. However, there is a paucity of data on whether G-CSF improves survival and prognosis in patients with decompensated cirrhosis.

Verma, Singh et al have shown in an open label trial that there was significantly better 12 month transplant free survival in ( GCSF+ Growth hormone + standard medical therapy group ) and ( G CSF + standard medical therapy group ) as compared to standard medical therapy group alone. CD 34+ cells at day 6 of therapy increased as compared to baseline. There was also a significant decrease of clinical scores, improvement in nutrition, better control of ascites, reduction in liver stiffness, lesser episodes of infection as well as improvement in QOL scores in the treatment groups having G CSF as compared to baseline.

In a recent study by Newsome et al, a multicentre, open label randomized phase 2 trial, patients were randomized to standard care, treatment with subcutaneous G CSF or treatment with G CSF for 5 days followed by leukaphersis and IV infusion of CD 133 positive haematopoietic stem cells. They did not find any difference in MELD score over time in all 3 treatment groups. Serious adverse effects were more common in the G CSF groups than in standard treatment group.

In a study by Kedarisetty CK et al. a significantly larger proportion of patients with decompensated cirrhosis given a combination of G-CSF \& Darbopoietin α survived for 12 months more than patients given only placebo ( 68% vs. 26.9%; P = 0.001 ). The combination therapy also reduced liver severity scores and sepsis to a greater extent than placebo.

In view of the conflicting results of the above studies and no studies on the use of multiple courses of GCSF in patients with decompensated cirrhosis in a double blind manner, the present study was undertaken to assess the safety and efficacy of G-CSF in patients with decompensated cirrhosis in the form of a double blinded RCT.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Efficacy and safety of anti-hepatic fibrosis drugs.
   Damiris K, Tafesh ZH, Pyrsopoulos N. · · 2020 · cited 30× · PMID 33244194 · DOI 10.3748/wjg.v26.i41.6304
2. Circulating neutrophil anti-pathogen dysfunction in cirrhosis.
   Balazs I, Stadlbauer V. · · 2023 · cited 9× · PMID 37822786 · DOI 10.1016/j.jhepr.2023.100871
3. Multiple cycles of granulocyte colony-stimulating factor in decompensated cirrhosis: a double-blind RCT.
   Venkitaraman A, De A, Verma N, Kumari S, et al · · 2022 · cited 9× · PMID 35322373 · DOI 10.1007/s12072-022-10314-x
4. Granulocyte colony-stimulating factor with or without stem or progenitor cell or growth factors infusion for people with compensated or decompensated advanced chronic liver disease.
   Colli A, Fraquelli M, Prati D, Casazza G. · · 2023 · cited 6× · PMID 37278488 · DOI 10.1002/14651858.cd013532.pub2
5. Enhancing hepatopathy clinical trial efficiency: a secure, large language model-powered pre-screening pipeline.
   Gui X, Lv H, Wang X, Lv L, et al · · 2025 · cited 1× · PMID 40517253 · DOI 10.1186/s13040-025-00458-5