Clinical trial NCT04431375: Efficacy of Addition of Fecal Microbiota Transplant (FMT) and Plasma Exchange to Tenofovir in Comparison to Monotherapy With Tenofovir in ACLF-HBV
Official title: Efficacy of Addition of Fecal Microbiota Transplant (FMT) and Plasma Exchange to Tenofovir in Comparison to Monotherapy With Tenofovir in ACLF-HBV
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Acute-On-Chronic Liver Failure
Hepatitis B
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2020-06-16
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 .

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

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival in both groups
timeFrame: Day 28
Secondary outcomes:
measure: Overall survival in both groups
timeFrame: 3 months
measure: Reduction in HBV DNA level
timeFrame: 14 days
measure: Reduction in HBV DNA level
timeFrame: 60 days
measure: Reduction in HBV DNA level
timeFrame: 90 days
measure: Reduction in CTP Score in both groups
timeFrame: 14 days
measure: Reduction in CTP Score in both groups
timeFrame: 30 days
measure: Reduction in CTP Score in both groups
timeFrame: 60 days
measure: Reduction in CTP Score in both groups
timeFrame: 90 days
measure: Reduction in MELD Score in both groups
timeFrame: 14 days
measure: Reduction in MELD Score in both groups
timeFrame: 30 days
measure: Reduction in MELD Score in both groups
timeFrame: 60 days
measure: Reduction in MELD Score in both groups
timeFrame: 90 days
measure: Percentage of patient's with improvement in hepatic failure calculated by MELD Na and CTP scores.
timeFrame: 14 days
measure: Percentage of patient's with improvement in hepatic failure calculated by MELD Na
timeFrame: 30 days
measure: Percentage of patient's with improvement in hepatic failure calculated by CTP scores.
timeFrame: 30 days
measure: Percentage of patient's with improvement in hepatic failure calculated by MELD Na
timeFrame: 60 days
measure: Percentage of patient's with improvement in hepatic failure calculated by CTP scores.
timeFrame: 60 days
measure: Percentage of patient's with improvement in hepatic failure calculated by MELD Na.
timeFrame: 90 days
measure: Percentage of patient's with improvement in hepatic failure calculated by CTP scores.
timeFrame: 90 days
measure: Change in microbiota profile in both groups
timeFrame: 10 days
measure: Change in microbiota profile in both groups
timeFrame: 30 days
measure: Change in microbiota profile in both groups
timeFrame: 60 days
measure: Change in microbiota profile in both groups
timeFrame: 90 days
measure: Change in plasma cytokine profile in both groups
timeFrame: 10 days
measure: Change in plasma cytokine profile in both groups
timeFrame: 28 days
measure: Change in plasma cytokine profile in both groups
timeFrame: 60 days
measure: Number of patients with adverse Events in both groups
timeFrame: 90 days
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of Liver & Biliary Sciences
state: Delhi
Study officials:
References: