Efficacy of Addition of Fecal Microbiota Transplant (FMT) and Plasma Exchange to Tenofovir in Comparison to Monotherapy With Tenofovir in ACLF-HBV
Primary Purpose
Acute-On-Chronic Liver Failure, Hepatitis B
Status
Recruiting
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Plasma Exchange
Tenofovir
Fecal Mircobiota Transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Acute-On-Chronic Liver Failure
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
Sites / Locations
- Institute of Liver & Biliary SciencesRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
plasma Exchange+Tenofovir+FMT
Tenofovir
Arm Description
Subjects will receive Plasma exchange 2 sessions alternate day followed by FMT for 7 days and Tenofovir [antiviral] 300mg PO once a day .
TabletTenofovir [antiviral] 300mg per oral once a day
Outcomes
Primary Outcome Measures
Overall survival in both groups
Secondary Outcome Measures
Overall survival in both groups
Reduction in HBV DNA level
Reduction in HBV DNA level
Reduction in HBV DNA level
Reduction in CTP Score in both groups
CTP Score ranges from 5 to 15 5=good 15=worst
Reduction in CTP Score in both groups
CTP Score ranges from 5 to 15 5=good 15=worst
Reduction in CTP Score in both groups
CTP Score ranges from 5 to 15 5=good 15=worst
Reduction in CTP Score in both groups
CTP Score ranges from 5 to 15 5=good 15=worst
Reduction in MELD Score in both groups
MELD Score ranges from 6 to 40 6=good 40=worst
Reduction in MELD Score in both groups
MELD Score ranges from 6 to 40 6=good 40=worst
Reduction in MELD Score in both groups
MELD Score ranges from 6 to 40 6=good 40=worst
Reduction in MELD Score in both groups
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.
Percentage of patient's with improvement in hepatic failure calculated by MELD Na
Percentage of patient's with improvement in hepatic failure calculated by CTP scores.
Percentage of patient's with improvement in hepatic failure calculated by MELD Na
Percentage of patient's with improvement in hepatic failure calculated by CTP scores.
Percentage of patient's with improvement in hepatic failure calculated by MELD Na.
Percentage of patient's with improvement in hepatic failure calculated by CTP scores.
Change in microbiota profile in both groups
Change in microbiota profile in both groups
Change in microbiota profile in both groups
Change in microbiota profile in both groups
Change in plasma cytokine profile in both groups
Change in plasma cytokine profile in both groups
Change in plasma cytokine profile in both groups
Number of patients with adverse Events in both groups
Full Information
NCT ID
NCT04431375
First Posted
June 4, 2020
Last Updated
January 27, 2022
Sponsor
Institute of Liver and Biliary Sciences, India
1. Study Identification
Unique Protocol Identification Number
NCT04431375
Brief Title
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
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 22, 2020 (Actual)
Primary Completion Date
June 10, 2022 (Anticipated)
Study Completion Date
June 10, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Liver and Biliary Sciences, India
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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 .
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute-On-Chronic Liver Failure, Hepatitis B
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
plasma Exchange+Tenofovir+FMT
Arm Type
Experimental
Arm Description
Subjects will receive Plasma exchange 2 sessions alternate day followed by FMT for 7 days and Tenofovir [antiviral] 300mg PO once a day .
Arm Title
Tenofovir
Arm Type
Active Comparator
Arm Description
TabletTenofovir [antiviral] 300mg per oral once a day
Intervention Type
Biological
Intervention Name(s)
Plasma Exchange
Intervention Description
Plasma exchange 2 sessions alternate day followed by FMT for 7 days and Tenofovir [antiviral] 300mg PO once a day .
Intervention Type
Drug
Intervention Name(s)
Tenofovir
Intervention Description
Tenofovir [antiviral] 300mg PO once a day .
Intervention Type
Other
Intervention Name(s)
Fecal Mircobiota Transplantation
Intervention Description
FMT for 7 days
Primary Outcome Measure Information:
Title
Overall survival in both groups
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
Overall survival in both groups
Time Frame
3 months
Title
Reduction in HBV DNA level
Time Frame
14 days
Title
Reduction in HBV DNA level
Time Frame
60 days
Title
Reduction in HBV DNA level
Time Frame
90 days
Title
Reduction in CTP Score in both groups
Description
CTP Score ranges from 5 to 15 5=good 15=worst
Time Frame
14 days
Title
Reduction in CTP Score in both groups
Description
CTP Score ranges from 5 to 15 5=good 15=worst
Time Frame
30 days
Title
Reduction in CTP Score in both groups
Description
CTP Score ranges from 5 to 15 5=good 15=worst
Time Frame
60 days
Title
Reduction in CTP Score in both groups
Description
CTP Score ranges from 5 to 15 5=good 15=worst
Time Frame
90 days
Title
Reduction in MELD Score in both groups
Description
MELD Score ranges from 6 to 40 6=good 40=worst
Time Frame
14 days
Title
Reduction in MELD Score in both groups
Description
MELD Score ranges from 6 to 40 6=good 40=worst
Time Frame
30 days
Title
Reduction in MELD Score in both groups
Description
MELD Score ranges from 6 to 40 6=good 40=worst
Time Frame
60 days
Title
Reduction in MELD Score in both groups
Description
MELD Score ranges from 6 to 40 6=good 40=worst
Time Frame
90 days
Title
Percentage of patient's with improvement in hepatic failure calculated by MELD Na and CTP scores.
Time Frame
14 days
Title
Percentage of patient's with improvement in hepatic failure calculated by MELD Na
Time Frame
30 days
Title
Percentage of patient's with improvement in hepatic failure calculated by CTP scores.
Time Frame
30 days
Title
Percentage of patient's with improvement in hepatic failure calculated by MELD Na
Time Frame
60 days
Title
Percentage of patient's with improvement in hepatic failure calculated by CTP scores.
Time Frame
60 days
Title
Percentage of patient's with improvement in hepatic failure calculated by MELD Na.
Time Frame
90 days
Title
Percentage of patient's with improvement in hepatic failure calculated by CTP scores.
Time Frame
90 days
Title
Change in microbiota profile in both groups
Time Frame
10 days
Title
Change in microbiota profile in both groups
Time Frame
30 days
Title
Change in microbiota profile in both groups
Time Frame
60 days
Title
Change in microbiota profile in both groups
Time Frame
90 days
Title
Change in plasma cytokine profile in both groups
Time Frame
10 days
Title
Change in plasma cytokine profile in both groups
Time Frame
28 days
Title
Change in plasma cytokine profile in both groups
Time Frame
60 days
Title
Number of patients with adverse Events in both groups
Time Frame
90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dr G. Srinivasa Reddy, MD
Phone
01146300000
Email
srinivasareddygolamari@gmail.com
Facility Information:
Facility Name
Institute of Liver & Biliary Sciences
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110070
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr G Srinivasa Reddy, MD
Phone
01146300000
Email
srinivasareddygolamari@gmail.com
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Efficacy of Addition of Fecal Microbiota Transplant (FMT) and Plasma Exchange to Tenofovir in Comparison to Monotherapy With Tenofovir in ACLF-HBV
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