- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT05195450
TAF (Tenofovir Alafenamide) for Preventing Progression of Liver Disease in Non-cirrhotic Chronic HBV Infection With Normal ALT and Low Viral Load.
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
The main goal of therapy for patients with chronic HBV infection with no significant liver disease is to improve survival and quality of life by preventing disease progression, development of liver cirrhosis and consequently HCC development. The likelihood of achieving these goals depends on the timing of therapy during the natural course of the infection but also on the stage of the disease and the patients' age when treatment is started. The inhibition of viral replication and normalization of ALT by antiviral treatment has been shown to achieve the elimination of chronic HBV-induced necroinflammatory activity and progressive fibrotic liver progression in the vast majority of patients, in turn reducing the risk of HCC. Even in HBeAg positive patients, treatment-induced HBeAg loss and seroconversion to antiHBe characterizes the induction of a partial immune control often leading to a low replicative phase of the chronic HBV infection and good outcomes.
Treatment in chronic HBV infection is indicated in - presence of advanced fibrosis/cirrhosis (LSM >11 KPA) or patients with significant fibrosis (LSM >8 or APRI >1.5 or >F2 on liver biopsy) with high viral load (>2000 IU/ml) or significantly elevated ALT (x2 ULN). Presence of any of these factors is known to increase the risk of development of cirrhosis and hepatocellular carcinoma. TAF in non-cirrhotic patients (LSM <8 KPA) with normal ALT and low viral load (HBV DNA <2000 IU/ml) (currently treatment ineligible) as compared to delayed initiation (on demand) might reduce HCC risk, progression of liver fibrosis and reduction in HBsAg levels. As TAF is known to have favorable effects on the overall long-term outcome, the main clinical challenge is to identify the patients at risk of HCC and cirrhosis who warrant early antiviral therapy.
연구 개요
상세 설명
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 label 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
- TAF 25 mg OD vs no treatment x 5 years and beyond
- Tests - Baseline - USG abdomen, ALT, Creatinine, DEXA, HBVDNA, HBeAg, HBsAg (quant), Fibroscan
- 6 monthly - ALT
- 1 yearly - USG abdomen, ALT, Creatinine, DEXA, HBVDNA, HBeAg, HBsAg (quant), Fibroscan
- 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.
연구 유형
등록 (예상)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: Dr Ankur Jindal, DM
- 전화번호: 01146300000
- 이메일: ankur.jindal3@gmail.com
연구 장소
-
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Delhi
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New Delhi, Delhi, 인도, 110070
- 모병
- Institute of Liver & Biliary Sciences (ILBS)
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연락하다:
- Dr Ankur Jindal, DM
- 전화번호: 01146300000
- 이메일: ankur.jindal3@gmail.com
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- HBsAg+
- Persistent normal ALT 3-6m apart (<30 IU/ml in male and <20 IU/ml in female)
- HBV DNA < 2000 IU/ml
- LSM <8 Kpa
Exclusion Criteria:
- Prior NUC/IFN exposure
- Renal dysfunction (Serum Creatinine >1.5 mg/dl)
- Known liver cirrhosis/ esophageal varices
- Any clinical decompensation (CD)
- Pre-existing hepatocellular carcinoma
- Pregnancy
- Healthcare workers (HCW)
- Post transplant, patients with advance malignancy or on chemotherapy
- Co-infections - Hepatitis C, Hepatitis D, Human immunodeficiency virus
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
---|---|
실험적: Tenofovir Alafenamide Fumarate
• TAF 25 mg OD vs no treatment x 5 years and beyond
|
• TAF 25 mg OD vs no treatment x 5 years and beyond
|
간섭 없음: No Treatment Arm
No treatment
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Percentage of patients with HBV DNA <2000 IU/ml, normal ALT and no significant fibrosis (as per APASL 2015).
기간: upto 5 Years
|
Any two of the following -
|
upto 5 Years
|
2차 결과 측정
결과 측정 |
기간 |
---|---|
Incidence of HCC
기간: upto 3 years
|
upto 3 years
|
Incidence of HCC
기간: upto 5 years
|
upto 5 years
|
Percentage of patients with LSM >8 Kpa
기간: upto 5 Years
|
upto 5 Years
|
Percentage of patients with LSM >11 Kpa
기간: upto 5 Years
|
upto 5 Years
|
Number of subjects with no progression of fibrosis
기간: upto 5 Years
|
upto 5 Years
|
Percentage of patients with APRI score >1.5 and >2
기간: upto 5 Years
|
upto 5 Years
|
Percentage of patients with HBV DNA >2000 IU/ml
기간: upto 5 Years
|
upto 5 Years
|
Percentage of patients with undetectable HBV DNA
기간: upto 5 Years
|
upto 5 Years
|
Percentage of patients with HBsAg loss and HBsAg seroconversion
기간: upto 5 Years
|
upto 5 Years
|
Log HBsAg reduction
기간: upto 5 Years
|
upto 5 Years
|
Percentage of patients with HBeAg loss and HBeAg seroconversion in HBeAg+ chronic hepatitis B
기간: upto 5 Years
|
upto 5 Years
|
Percentage of patients with ALT > ULN, >2 times and 5 times ULN
기간: upto 5 Years
|
upto 5 Years
|
Treatment related adverse effects of TAF
기간: upto 5 Years
|
upto 5 Years
|
Non-compliant to treatment or monitoring
기간: upto 5 years
|
upto 5 years
|
Death
기간: upto 5 years
|
upto 5 years
|
Treatment related severe adverse effects
기간: upto 5 years
|
upto 5 years
|
공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (예상)
연구 완료 (예상)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- ILBS-HBV-02
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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