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Study Comparing the Safety of Switching From Lamivudine to Adefovir Dipivoxil Versus Overlapping Lamivudine and Adefovir Before Adefovir Dipivoxil Monotherapy in Patients With Chronic Hepatitis B

2021년 11월 5일 업데이트: Thomas Jefferson University

A Single Center Open-Label, Randomized Study Comparing the Safety of Immediately Switching From Lamivudine to Adefovir Dipivoxil Versus Overlapping Lamivudine and Adefovir for 12 Weeks Before Instituting Adefovir Dipivoxil Monotherapy in Patients With Chronic Hepatitis B

In earlier clinical studies, when patients who have been on lamivudine (LAM) were switched to adefovir dipivoxil (ADV), some patients developed ALT flares with an elevation of ALT > 10 x the upper limits of normal (ULN).

There were no cases of hepatic decompensation with the flares, however. The transition methods were varied among physicians from no overlapping to overlapping for 1 to 3 months with LAM and ADV. There is still some uncertainty about the optimal approach to switching from LAM to ADV.

This study will compare the safety of directly switching to ADV to a protocolled switch after a period of overlap of 12 weeks. This will facilitate pro-active switching in patients on LAM and will also highlight genotypic resistance ahead of phenotypic resistance as a reason to switch patients. Data to date have only been presented as part of a controlled study in patients with clinically evident LAM-resistance. This study will enroll patients who still have serum hepatitis B virus (HBV) DNA suppression whilst receiving LAM.

연구 개요

상태

완전한

상세 설명

Chronic HBV infection is an important worldwide cause of morbidity, mortality and source of potential new infections. There are an estimated 350 million carriers of HBV in the world. In China, Southeast Asia and sub-Saharan Africa, as many as 10-15% of the population are chronically infected. In North America and Northern Europe, infection and carrier rates are much lower, usually below 1%. Intermediate carrier rates of 1-5% are found in Southern Europe (e.g., Italy, Greece and Spain), parts of South and Central America, the Middle East and Japan. Persistent infection develops in over 90% of perinatally infected children and in 3-10% of people who become infected after the age of 6 years. Worldwide, it has been estimated that more than one million people die annually due to HBV-related end stage diseases such as cirrhosis and hepatocellular carcinoma.

The goal of antiviral therapy for hepatitis B is to reduce a patient's risks for progressive liver disease through prolonged suppression or eradication of HBV infection and to arrest or ameliorate HBV-related liver damage.

연구 유형

중재적

등록 (실제)

40

단계

  • 4단계

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  • Males and females ≥ 18 years of age with chronic hepatitis B
  • Hepatitis B surface antigen (HBsAg)(+) for a minimum of 6 months prior to entry
  • Hepatitis B envelope antigen (HBeAg)(+) or (-) at baseline
  • Patients having previously received LAM for at least 24 weeks
  • Patients with compensated liver function (Child-Pugh score ≤ 6)

Exclusion Criteria:

  • Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with patient treatment, assessment or compliance with the protocol.
  • Received immunoglobulins, interferon or other immune or cytokine-based therapies with possible activity in hepatitis B disease within 6 months prior to study screening.
  • Organ or bone marrow transplant recipients.
  • Evidence of active liver disease due to other causes (e.g., Wilson's disease, hemochromatosis, autoimmune hepatitis, hepatitis C or hepatitis D co-infection)
  • Patients taking parenteral (intravenous or intramuscular or subcutaneous) or oral steroids, immuno-suppressant therapies or chemotherapeutic agents within 2 months of study screening or expected to receive these agents during the course of the study.
  • Previous participation in an investigational trial involving administration of any investigational compound within 2 months prior to the study screening or those who received anti-HBV therapy other than lamivudine within the previous 3 months (e.g. anabolic steroids, ketaconazole, itraconazole, isoniazid, rifampin, rifabutin, simvastatin, lovastatin)
  • Clinically relevant alcohol or drug use or history of alcohol or drug use considered by the investigator to be sufficient to hinder compliance with treatment, follow up procedures or evaluation of adverse events
  • Lactating females or females with a positive serum pregnancy test.
  • Females of childbearing potential (post-puberty) unwilling or unable to have pregnancy testing at any study visit
  • Therapy with nephrotoxic drugs (e.g. aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cisplatin pentamidine, tacrolimus, cyclosporine) or competitors of renal excretion (e.g. probenecid) within 2 months prior to study screening or the expectation that subject will receive these during the course of the study.
  • The use of antiviral therapy with agents demonstrating potential anti-HBV activity other than lamivudine within the previous 3 months (e.g. famciclovir, lobucavir, emtricitabine, DAPD, L-FMAU, entecavir, ganciclovir or others).
  • History of hypersensitivity to nucleoside and/or nucleotide analogues.
  • Clinical, ultrasonographic or radiologic evidence of hepatic mass suggestive of hepatocellular carcinoma.
  • Serum alphafetoprotein (AFP) > 50 ng/mL at the first screening visit. However, if the AFP level is > 50 ng/mL at the first screening visit, but has remained stable or decreased over the 6 months preceding the first screening visit, and if there is no radiologic or ultrasonic evidence of hepatic mass(es) suggestive of hepatocellular carcinoma, the patient will be allowed to enroll.
  • Inability to comply with study requirements.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

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
활성 비교기: Direct switch to Adefovir Dipivoxil from Lamivudine
활성 비교기: Overlapping Lamivudine and Adefovir Dipivoxil for 3 months followed by ADV monotherapy

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
기간
Observe the proportion of patients with ALT elevations (> 10 x ULN) at any time over the course of the switch
기간: baseline, 3, 6, 9, and 12 months
baseline, 3, 6, 9, and 12 months
Study serum HBV DNA levels over time
기간: baseline, 3, 6, 9, and 12 months
baseline, 3, 6, 9, and 12 months
Study serum ALT levels over time
기간: baseline, 3, 6, 9, and 12 months
baseline, 3, 6, 9, and 12 months
Study the proportion of patients with YMDD variants at entry
기간: baseline, 3, 6, 9, and 12 months
baseline, 3, 6, 9, and 12 months
Study the safety during the switching period
기간: baseline, 3, 6, 9, and 12 months
baseline, 3, 6, 9, and 12 months

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

수사관

  • 수석 연구원: Hie-Won Hann, M.D., Thomas Jefferson University

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2005년 6월 17일

기본 완료 (실제)

2009년 2월 1일

연구 완료 (실제)

2009년 2월 5일

연구 등록 날짜

최초 제출

2006년 3월 24일

QC 기준을 충족하는 최초 제출

2006년 3월 24일

처음 게시됨 (추정)

2006년 3월 27일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2021년 11월 12일

QC 기준을 충족하는 마지막 업데이트 제출

2021년 11월 5일

마지막으로 확인됨

2021년 11월 1일

추가 정보

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다