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

NCT ID: NCT04431375

Last Updated: 2022-01-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-22

Study Completion Date

2022-06-10

Brief Summary

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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

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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

Conditions

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Acute-On-Chronic Liver Failure Hepatitis B

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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 .

Group Type EXPERIMENTAL

Plasma Exchange

Intervention Type BIOLOGICAL

Plasma exchange 2 sessions alternate day followed by FMT for 7 days and Tenofovir \[antiviral\] 300mg PO once a day .

Tenofovir

Intervention Type DRUG

Tenofovir \[antiviral\] 300mg PO once a day .

Fecal Mircobiota Transplantation

Intervention Type OTHER

FMT for 7 days

Tenofovir

TabletTenofovir \[antiviral\] 300mg per oral once a day

Group Type ACTIVE_COMPARATOR

Tenofovir

Intervention Type DRUG

Tenofovir \[antiviral\] 300mg PO once a day .

Interventions

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Plasma Exchange

Plasma exchange 2 sessions alternate day followed by FMT for 7 days and Tenofovir \[antiviral\] 300mg PO once a day .

Intervention Type BIOLOGICAL

Tenofovir

Tenofovir \[antiviral\] 300mg PO once a day .

Intervention Type DRUG

Fecal Mircobiota Transplantation

FMT for 7 days

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institute of Liver and Biliary Sciences, India

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Institute of Liver & Biliary Sciences

New Delhi, National Capital Territory of Delhi, India

Site Status RECRUITING

Countries

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India

Central Contacts

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Dr G. Srinivasa Reddy, MD

Role: CONTACT

01146300000

Facility Contacts

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Dr G Srinivasa Reddy, MD

Role: primary

01146300000

Other Identifiers

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ILBS-ACLF-05

Identifier Type: -

Identifier Source: org_study_id

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