Efficacy of Addition of Fecal Microbiota Transplant (FMT) and Plasma Exchange to Tenofovir in Comparison to Monotherapy With Tenofovir in ACLF-HBV
Study Details
Study Description
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 .
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
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
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Hypocalcemia
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Hypokalemia
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Metabolic alkalosis
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Hypotension
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Anaphylaxis
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TRALI TENOFOVIR Tenofovir
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Reversible proximal renal tubular toxicity.
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Reduced bone mineral density
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Manifestations of mitochondrial toxicity (i.e., neuropathy, myopathy, lactic acidosis
Stopping rule of study:
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Allergic reactions except mild drug reactions
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Arterial hypotension or development of shock /Hypertension
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Arrhythmias
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Development or progression of organ failures during therapy
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Transfusion related lung injury
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Uncontrolled Bleeding or DIC
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Severe dyselectrolytemia( k+<2.5 or >5.5)
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Seizures/tetany
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Patients who are undergoing or listed for Transplantation
Study Design
Arms and Interventions
| 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 .
|
Outcome Measures
Primary Outcome Measures
- Overall survival in both groups [Day 28]
Secondary Outcome Measures
- 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 [14 days]
CTP Score ranges from 5 to 15 5=good 15=worst
- Reduction in CTP Score in both groups [30 days]
CTP Score ranges from 5 to 15 5=good 15=worst
- Reduction in CTP Score in both groups [60 days]
CTP Score ranges from 5 to 15 5=good 15=worst
- Reduction in CTP Score in both groups [90 days]
CTP Score ranges from 5 to 15 5=good 15=worst
- Reduction in MELD Score in both groups [14 days]
MELD Score ranges from 6 to 40 6=good 40=worst
- Reduction in MELD Score in both groups [30 days]
MELD Score ranges from 6 to 40 6=good 40=worst
- Reduction in MELD Score in both groups [60 days]
MELD Score ranges from 6 to 40 6=good 40=worst
- Reduction in MELD Score in both groups [90 days]
MELD Score ranges from 6 to 40 6=good 40=worst
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age - 18-75 years
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Patients with ACLF - HBV reactivation according to APASL guidelines.
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MELD < 30 WITH AKI,HE
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MELD < 30 WITH OUT EXTRAHEPATIC FAILURE
Exclusion Criteria:
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MELD > 30
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Co existing hepatitis A,E,D
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HCC
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Sepsis
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Alcohol intake, substance abuse, HIV, IBD, chronic constipation or diarrhoea
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Allergy to plasma, protamine or heparin,
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Active hemorrhage or disseminated intravascular coagulation (DIC)
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Unstable hemodynamics (e.g., blood pressure <90/60 mmHg, heart rate >100 bpm),
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Cerebral or myocardiac infarction
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Pregnancy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institute of Liver & Biliary Sciences | New Delhi | Delhi | India | 110070 |
Sponsors and Collaborators
- Institute of Liver and Biliary Sciences, India
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ILBS-ACLF-05