| CTRI Number |
CTRI/2022/01/039541 [Registered on: 18/01/2022] Trial Registered Prospectively |
| Last Modified On: |
23/02/2022 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
TAF (drug) for hepatitis B virus infection |
|
Scientific Title of Study
|
TAF (Tenofovir Alafenamide) for preventing progression of liver disease in non-cirrhotic chronic HBV infection with normal ALT and low viral load – a randomized controlled trial. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Ankur Jindal |
| Designation |
Associate Professor,Hepatology |
| Affiliation |
Institute of Liver and Biliary Sciences |
| Address |
Room No 23347, Department of Hepatology, Phase II, 3rd Floor,D-1, Vasant Kunj New Delhi-110070.
South West
DELHI
110070
India |
| Phone |
|
| Fax |
|
| Email |
ankur.jindal3@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Ankur Jindal |
| Designation |
Associate Professor,Hepatology |
| Affiliation |
Institute of Liver and Biliary Sciences |
| Address |
Room No 23347, Department of Hepatology, Phase II, 3rd Floor,D-1, Vasant Kunj New Delhi-110070.
DELHI
110070
India |
| Phone |
|
| Fax |
|
| Email |
ankur.jindal3@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Ankur Jindal |
| Designation |
Associate Professor,Hepatology |
| Affiliation |
Institute of Liver and Biliary Sciences |
| Address |
Room No 23347, Department of Hepatology, Phase II, 3rd Floor,D-1, Vasant Kunj New Delhi-110070.
DELHI
110070
India |
| Phone |
|
| Fax |
|
| Email |
ankur.jindal3@gmail.com |
|
|
Source of Monetary or Material Support
|
| Institute of Liver and Biliary Sciences, D-1,Vasant Kunj, New Delhi-110070 |
|
|
Primary Sponsor
|
| Name |
Institute of Liver and Biliary Sciences |
| Address |
D-1,Vasant Kunj, New Delhi-110070 |
| Type of Sponsor |
Government medical college |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Ankur Jindal |
Institute of Liver and Biliary Sciences |
Room No 23347, Department of Hepatology, Phase II, 3rd Floor,Institute of Liver and Biliary Sciences, D-1, Vasant Kunj New Delhi-110070.
South West
DELHI |
01146300000
ankur.jindal3@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee, ILBS |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K77||Liver disorders in diseases classified elsewhere, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
No intervention |
No intervention |
| Intervention |
Tenofovir Alafenamide Fumarate |
TAF once daily for 5 years per oral |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
1. HBsAg+
2. Persistent normal ALT 3-6m apart (<30 IU/ml in male and <20 IU/ml in female)
3. HBV DNA < 2000 IU/ml
4. LSM <8 Kpa
|
|
| ExclusionCriteria |
| Details |
1.Prior NUC/IFN exposure.
2.Renal dysfunction (Serum Creatinine >1.5
mg/dl).
3.Known liver cirrhosis/ esophageal varices.
4.Any clinical decompensation (CD).
5.Pre-existing hepatocellular carcinoma.
6.Pregnancy
7.Healthcare workers (HCW).
8.Post transplant, patients with advance
malignancy or on chemotherapy.
9.Co-infections – Hepatitis C, Hepatitis D,
Human immunodeficiency virus. |
|
|
Method of Generating Random Sequence
|
Permuted block randomization, fixed |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
Percentage of patients with HBV DNA less than 2000 IU/ml, normal ALT and no significant fibrosis (as per APASL 2015)
Any two of the following –
1. Significant fibrosis (LSM more than 8 Kpa or APRI more than 1.5)
2. Persistently elevated ALT (2 consecutive ALT more than 30 U/ml 3-6m apart)
3. HBV DNA more than 2000 IU/ml
|
upto 5 years |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Incidence of HCC |
upto 3 years and 5 years |
| Percentage of patients with LSM more than 8 Kpa (significant fibrosis) |
upto 5 years |
| Percentage of patients with LSM more than 11 Kpa (cirrhosis) |
upto 5 years |
| No progression of fibrosis (reduction in LSM value) |
upto 5 years |
| Percentage of patients with APRI score more than 1.5 and more than 2 |
upto 5 years |
| Percentage of patients with HBV DNA more than 2000 IU/ml |
upto 5 years |
| Percentage of patients with undetectable HBV DNA |
upto 5 years |
| Percentage of patients with HBsAg loss and HBsAg seroconversion |
upto 5 years |
| Log HBsAg reduction |
upto 5 years |
| Percentage of patients with HBeAg loss and HBeAg seroconversion in HBeAg positive chronic hepatitis B |
upto 5 years |
| Percentage of patients with ALT more than ULN, more than 2 times and 5 times ULN |
upto 5 years |
| Treatment related adverse effects of TAF |
upto 5 years |
| Non-compliant to treatment or monitoring |
upto 5 years |
| Death |
upto 5 years |
| Treatment related severe adverse effects |
upto 5 years |
|
|
Target Sample Size
|
Total Sample Size="200"
Sample Size from India="200"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
18/01/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="5"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Aim and Objective –
To study the safety and efficacy
of TAF as compared to initiation based on current criteria in patients with
non-cirrhotic chronic HBV infection and normal ALT and low viral load.
Methodology:
Study population: The study will
be conducted on the treatment naïve consecutive patients having non-cirrhotic
chronic HBV infection and normal ALT and low viral load seen at the outpatient
clinics/wards of Department of Hepatology, ILBS, New Delhi.
Study Design: A Prospective,
Randomized, Single Center Open Labelled Study.
Study Period: 5 years from the
last patient enrollment
Sample Size with justification:
All consecutive cases consenting to be a participant in this study and meeting
inclusion and exclusion criteria will be enrolled. Considering the incidence of
20% for the composite end-point in patients without TAF and 5% for patients on
TAF, with power of 80% and alpha error of 5%, 176 patients (88 patients in each
arm) need to be enrolled. Considering the attrition rate of ~15%, we decide to
enroll 100 patients in each arm.
Intervention
1. TAF
25 mg OD vs no treatment x 5 years and beyond
2. Tests
– Baseline – USG abdomen, ALT, Creatinine, DEXA, HBVDNA, HBeAg, HBsAg (quant),
Fibroscan
3. 6
monthly – ALT
4. 1
yearly - USG abdomen, ALT, Creatinine, DEXA, HBVDNA, HBeAg, HBsAg (quant),
Fibroscan
5. No
liver biopsy
Statistical Analysis: Data will
be reported as mean + SD. Categorical variables will be compared using the
chi-square test or Fisher exact test. Normal continuous variables will be
compared using the Student’s t test Non normal continuous variables will be
compared using the Mann Whitney rank-sum test (unpaired data) or the Wilcoxon
test (paired data). The actuarial probability of survival will be calculated by
the Kaplan-Meier method and compared using the log-rank test. A Cox regression
analysis will be performed to identify independent prognostic factors for
survival. Univariate and multivariate analysis will be used whenever applicable.
Adverse effects: Most common-
headache, nausea, and fatigue; (1% to 10%): Abdominal pain, nausea, diarrhea,
dyspepsia, elevated serum amylase, vomiting, flatulence, abdominal distension;
Common (1% to 10%): Rash, pruritus, elevated ALT; Uncommon (0.1% to 1%):
Treatment ALT flares. |