Efficacy of Addition of Fecal Microbiota Transplant (FMT) and Plasma Exchange to Tenofovir in Comparison to Monotherapy With Tenofovir in ACLF-HBV

A randomized controlled trial to study the efficacy of addition of FMT & plasma exchange to tenofovir compared to monotherapy with tenofovir in patients with HBV reactivation who develops Acute on chronic liver failure.

In this study the patients who meet the inclusion criteria will be randomized to either receive Tenofovir or with FMT + plasma exchange along with Tenofovir . Blood samples & stool samples will be taken & analysis will be done accordingly .The patients are followed for 90 days MELD,APACHE & SOFA scores are calculated.Then statistical analysis will be done to find whether the addition of plasma exchange & FMT adds benefit compared to tenofovir treatment alone .

Study Overview

• Status: Recruiting
• Conditions: Acute-On-Chronic Liver Failure; Hepatitis B
• Intervention / Treatment: Biological: Plasma Exchange; Drug: Tenofovir; Other: Fecal Mircobiota Transplantation

Detailed Description

A randomized controlled trial to study the efficacy of addition of FMT & plasma exchange to tenofovir compared to monotherapy with tenofovir in patients with HBV reactivation who develops Acute on chronic liver failure.

In this study the patients who meet the inclusion criteria will be randomized to either receive Tenofovir or with FMT + plasma exchange along with Tenofovir . Blood samples & stool samples will be taken & analysis will be done accordingly .The patients are followed for 90 days MELD,APACHE & SOFA scores are calculated.Then statistical analysis will be done to find whether the addition of plasma exchange & FMT adds benefit compared to tenofovir treatment alone .

Study period: 2 Years

Intervention:

The patients in Group A will receive T.Tenofovir [antiviral] 300mg per oral once a day .

The patients in Group B will receive Plasma exchange 2 sessions alternate day followed by FMT for 7 days and Tenofovir [antiviral] 300mg PO once a day .

Intravenous antibiotics will be given to all patients included in study empirically, because of high risk of infection in these patients. Patients with sepsis are excluded from the study.

Methodology for FMT - Fresh Stool [30 g] is obtained from donor <3 hr before FMT. 150 mL sterile 0.9N saline is added to sample & homogenized in a blender. It is Continued 3 times in pulses of 20-30 secs, till homogenous suspension. Slow filtration is done with membrane filter (330µm) to give adequate time. Filtration is repeated 3 times. Patient is kept NPO for 4 hrs. prior to the instillation .100 ml of fresh filtrate is given for 7 days through naso-jejunal tube over 5-10 minutes .Patient is kept reclined at 45° for 4 hr. Normal diet is given after 2 hr of procedure. IV antibiotics are continued as per institutional protocol in case of sepsis.

Methodology for plasma exchange [PE] - Circulatory access will be established through a double lumen catheter via the patient's femoral vein. The total exchanged plasma volume will be 2500-3500 mL, and the Plasma Exchange rate will be 20-25 mL/min. Fresh-frozen plasma (FFP) will be supplied by the ILBS Blood Bank. Dexamethasone (5 mg) and heparin (2500 U) will be injected routinely before PE. Heparin will be neutralized at the end of PE by an injection of 20-50 mg protamine sulfate. PE will be repeated alternate day for a total of 2 sessions Adverse effects: FMT FMT - Sore throat and difficulty in deglutition secondary to naso-gastric tube insertion Plasma exchange PE

• Hypocalcemia
• Hypokalemia
• Metabolic alkalosis
• Hypotension
• Anaphylaxis
• TRALI TENOFOVIR Tenofovir
• Reversible proximal renal tubular toxicity.
• Reduced bone mineral density
• Manifestations of mitochondrial toxicity (i.e., neuropathy, myopathy, lactic acidosis

Stopping rule of study:

• Allergic reactions except mild drug reactions
• Arterial hypotension or development of shock /Hypertension
• Arrhythmias
• Development or progression of organ failures during therapy
• Transfusion related lung injury
• Uncontrolled Bleeding or DIC
• Severe dyselectrolytemia( k+<2.5 or >5.5)
• Seizures/tetany
• Patients who are undergoing or listed for Transplantation

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Recruiting
      • Institute of Liver & Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age - 18-75 years
• Patients with ACLF - HBV reactivation according to APASL guidelines.
• MELD < 30 WITH AKI,HE
• MELD < 30 WITH OUT EXTRAHEPATIC FAILURE

Exclusion Criteria:

• MELD > 30
• Co existing hepatitis A,E,D
• HCC
• Sepsis
• Alcohol intake, substance abuse, HIV, IBD, chronic constipation or diarrhoea
• Allergy to plasma, protamine or heparin,
• Active hemorrhage or disseminated intravascular coagulation (DIC)
• Unstable hemodynamics (e.g., blood pressure <90/60 mmHg, heart rate >100 bpm),
• Cerebral or myocardiac infarction
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: plasma Exchange+Tenofovir+FMT; Subjects will receive Plasma exchange 2 sessions alternate day followed by FMT for 7 days and Tenofovir [antiviral] 300mg PO once a day .	Biological: Plasma Exchange; Plasma exchange 2 sessions alternate day followed by FMT for 7 days and Tenofovir [antiviral] 300mg PO once a day .; Drug: Tenofovir; Tenofovir [antiviral] 300mg PO once a day .; Other: Fecal Mircobiota Transplantation; FMT for 7 days
ACTIVE_COMPARATOR: Tenofovir; TabletTenofovir [antiviral] 300mg per oral once a day	Drug: Tenofovir; Tenofovir [antiviral] 300mg PO once a day .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival in both groups	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival in both groups		3 months
Reduction in HBV DNA level		14 days
Reduction in HBV DNA level		60 days
Reduction in HBV DNA level		90 days
Reduction in CTP Score in both groups	CTP Score ranges from 5 to 15 5=good 15=worst	14 days
Reduction in CTP Score in both groups	CTP Score ranges from 5 to 15 5=good 15=worst	30 days
Reduction in CTP Score in both groups	CTP Score ranges from 5 to 15 5=good 15=worst	60 days
Reduction in CTP Score in both groups	CTP Score ranges from 5 to 15 5=good 15=worst	90 days
Reduction in MELD Score in both groups	MELD Score ranges from 6 to 40 6=good 40=worst	14 days
Reduction in MELD Score in both groups	MELD Score ranges from 6 to 40 6=good 40=worst	30 days
Reduction in MELD Score in both groups	MELD Score ranges from 6 to 40 6=good 40=worst	60 days
Reduction in MELD Score in both groups	MELD Score ranges from 6 to 40 6=good 40=worst	90 days
Percentage of patient's with improvement in hepatic failure calculated by MELD Na and CTP scores.		14 days
Percentage of patient's with improvement in hepatic failure calculated by MELD Na		30 days
Percentage of patient's with improvement in hepatic failure calculated by CTP scores.		30 days
Percentage of patient's with improvement in hepatic failure calculated by MELD Na		60 days
Percentage of patient's with improvement in hepatic failure calculated by CTP scores.		60 days
Percentage of patient's with improvement in hepatic failure calculated by MELD Na.		90 days
Percentage of patient's with improvement in hepatic failure calculated by CTP scores.		90 days
Change in microbiota profile in both groups		10 days
Change in microbiota profile in both groups		30 days
Change in microbiota profile in both groups		60 days
Change in microbiota profile in both groups		90 days
Change in plasma cytokine profile in both groups		10 days
Change in plasma cytokine profile in both groups		28 days
Change in plasma cytokine profile in both groups		60 days
Number of patients with adverse Events in both groups		90 days

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 22, 2020
• Primary Completion (ANTICIPATED): June 10, 2022
• Study Completion (ANTICIPATED): June 10, 2022

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 12, 2020
• First Posted (ACTUAL): June 16, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2022
• Last Update Submitted That Met QC Criteria: January 27, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Liver Failure, Acute; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; End Stage Liver Disease; Liver Failure; Acute-On-Chronic Liver Failure; Hepatitis B; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: ILBS-ACLF-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No