CLINICAL TRIAL: THE HEPATITIS C ANTIVIRAL LONG-TERM TREATMENT AGAINST CIRRHOSIS

临床试验：丙型肝炎抗病毒药物长期治疗肝硬化

• 批准号: 7731230
• 负责人: Jules Leonard Dienstag
• 金额: $ 0.42万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7731230
• 关键词: Adverse effects; Antiviral Agents; Biopsy; Cirrhosis; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Development; Disease Progression; End Point; Enrollment; Fibrosis; Funding; Grant; Hepatitis; Hepatitis C virus; Histologic; Institution; Interferons; Living Wills; Longitudinal Studies; Numbers; Participant; Patients; Population Study; Quality of life; RNA; Randomized; Research; Research Design; Research Personnel; Resources; Ribavirin; Risk; Serum; Source; Therapeutic; Time; Treatment Protocols; United States National Institutes of Health; Virus; Week; base; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The aim of the present study is to determine whether prolonged interferon-based therapy can be achieved and maintained in a reasonable number of subjects over several years' time, and whether the anticipated benefits are worth the risk and expense involved. The study population will be limited to those at highest risk of progression to cirrhosis or its complications, namely, patients with established fibrosis or cirrhosis on biopsy at study entry. Since all patients enrolled will have had different previous treatments, the present study design provides that all patients entering the long-term portion of the study have begun at a common starting point and have had a second chance at reaching a sustained virologic response. In the initial course of therapy all patients will be treated with peginterferon plus ribavirin for a period of 24 weeks, with virologic assessment at 20 weeks to refute their nonresponder status. Thus, patients entering the long-term study will know that they have been given the very latest regimen in an attempt to achieve virologic clearance and, having failed, now can be certain that they are non-responders to conventional therapy. It is anticipated that approximately 20% will have no detectable virus in serum at the 20 week point, and that this group may continue treatment and receive a full course of 48 weeks' therapy. Those who remain HCV-positive in serum at 20 weeks will be randomized to receive either continued peginterferon (without further ribavirin) or no further treatment beyond careful observation for the ensuing 3 and 1/2 years. Week 20 responders who develop detectable HCV RNA at weeks 36, 48, 60 or 72 may be randomized to receive either continued peginterferon (without further ribavirin) or no further treatment beyond careful observation for an additional 42 months. Therapeutic endpoints will be of two types: histologic progression of disease as well as development of evidence of cirrhotic decompensation. The extent of side effects of interferon as well as a detailed assessment of quality of life will be obtained for all study participants.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的目的是确定是否可以在合理数量的受试者中实现并维持基于干扰素的长期治疗数年，以及预期的益处是否值得所涉及的风险和费用。研究人群将限于进展为肝硬化或其并发症风险最高的患者，即入组研究时活检证实存在纤维化或肝硬化的患者。由于入组的所有患者既往均接受过不同的治疗，因此本研究设计规定，进入长期研究部分的所有患者均从共同的起点开始，并有第二次机会达到持续的病毒学应答。在最初的治疗过程中，所有患者都将接受聚乙二醇干扰素加利巴韦林治疗24周，在20周时进行病毒学评估以反驳其无应答状态。因此，进入长期研究的患者将知道他们已经接受了最新的治疗方案，试图实现病毒学清除，如果失败，现在可以确定他们对常规治疗无应答。预计约20%的患者在20周时血清中没有可检测到的病毒，该组患者可以继续治疗并接受48周的完整疗程。那些在20周时血清中HCV仍然阳性的患者将随机接受持续的聚乙二醇干扰素（没有进一步的利巴韦林）或在随后的3年和1/2年内仔细观察后不再进一步治疗。第20周应答者在第36、48、60或72周出现可检测到的HCV RNA，可随机接受持续聚乙二醇干扰素（不进一步利巴韦林）或不进一步治疗，超过仔细观察42个月。 治疗终点有两种类型：疾病的组织学进展以及出现血小板失代偿的证据。将获得所有研究参与者的干扰素副作用程度以及生活质量的详细评估。