Safety and Effectiveness of Raltegravir Plus Darunavir/Ritonavir in Treatment-Naive HIV-Infected Adults
2018年10月11日 更新者：AIDS Clinical Trials Group
A Pilot Efficacy and Safety Trial of Raltegravir Plus Darunavir/Ritonavir for Treatment-Naive HIV-1-Infected Subjects
The purpose of this study is to assess the effectiveness and safety of an antiretroviral therapy (ART) regimen consisting of raltegravir (RAL) and darunavir (DRV)/ritonavir (RTV) as first-line therapy in treatment-naïve participants.
研究概览
详细说明
Despite the remarkable strides made in the treatment of HIV-1-infected persons over the last decade, current first-line ART regimens are imperfect. The ideal combination, unlike some current first-line options, would have uncompromised efficacy in the presence of transmitted drug-resistant variants. The primary purpose of this study is to estimate the cumulative proportion of ART-naive participants experiencing virologic failure at or prior to week 24 after initiating raltegravir (RAL) plus darunavir/ritonavir (DRV/RTV).
The study will last 52 weeks. All participants will follow the same treatment schedule and take RAL plus DRV/RTV orally daily for the duration of the trial.
After entry, all participants will have scheduled visits at weeks 1, 4, 12, 24, 36, 48, and 52. Medical/medication history, blood and urine collection, and liver function tests will occur at screening. A targeted physical exam and concomitant medications history will occur at all study visits. Blood and urine collection and liver function tests will occur at most study visits. For females, a pregnancy test will occur at screening and study entry.
RAL and DRV were provided by the study. RTV was not provided by the study.
研究类型
介入性
注册 (实际的)
113
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Alabama
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Birmingham、Alabama、美国、35294
- AlabamaTherapeutics CRS
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California
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Palo Alto、California、美国、94304
- Stanford CRS
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San Diego、California、美国、92103
- Ucsd, Avrc Crs
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San Francisco、California、美国、94110
- Ucsf Aids Crs
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Colorado
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Aurora、Colorado、美国、80045
- University of Colorado Hospital CRS
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District of Columbia
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Washington、District of Columbia、美国、20007
- Georgetown University CRS
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Illinois
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Chicago、Illinois、美国、60611
- Northwestern University CRS
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Massachusetts
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Boston、Massachusetts、美国、02115
- Beth Israel Deaconess Med Center
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Boston、Massachusetts、美国、02115
- Brigham and Women's Hosp. ACTG CRS
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Missouri
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Saint Louis、Missouri、美国、63110
- Washington U CRS
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New York
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Rochester、New York、美国、14604
- AIDS Community Health Ctr. ACTG CRS
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North Carolina
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Chapel Hill、North Carolina、美国、27599
- Unc Aids Crs
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Durham、North Carolina、美国、27710
- Duke Univ. Med. Ctr. Adult CRS
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Ohio
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Cincinnati、Ohio、美国、45267-0405
- Univ. of Cincinnati CRS
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Cleveland、Ohio、美国、44106
- Case CRS
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Cleveland、Ohio、美国、44109
- MetroHealth CRS
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Columbus、Ohio、美国、43210
- The Ohio State Univ. AIDS CRS
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Pennsylvania
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Philadelphia、Pennsylvania、美国、19104
- Hosp. of the Univ. of Pennsylvania CRS
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Pittsburgh、Pennsylvania、美国、15213
- University of Pittsburgh CTU
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Rhode Island
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Providence、Rhode Island、美国、02906
- The Miriam Hospital
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Tennessee
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Nashville、Tennessee、美国、37203
- Vanderbilt Therapeutics CRS
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Texas
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Houston、Texas、美国、77030
- Houston AIDS Research Team
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- HIV-1-infected
- Plasma HIV-1 RNA of at least 5,000 copies/mL within 90 days prior to study entry
- HIV genotype (for reverse transcriptase and protease) performed at any time prior to study entry. More information on this criterion can be found in the protocol.
- ARV drug-naive. More information on this criterion can be found in the protocol.
- Negative result from a hepatitis B surface antigen test performed within 90 days prior to study entry
- Agree to use one form of medically-accepted contraceptive throughout the study and for 60 days after stopping study treatment. More information on this criterion can be found in the protocol.
Exclusion Criteria:
- Serious illness requiring systemic treatment and/or hospitalization for at least 7 days prior to study. More information on this criterion can be found in the protocol.
- Screening HIV genotype obtained any time prior to study entry with more than one DRV resistance-associated mutation [RAM] (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, I84V, and L89V) or L76V alone
- Known major integrase inhibitor RAM(s), including N155H, Q148H/R/K, Y143C/R, and G140S
- Severe renal insufficiency requiring hemodialysis or peritoneal dialysis
- Treatment with immunomodulators within 30 days prior to study entry. More information on this criterion can be found in the protocol.
- Current medications that are prohibited with any study medications. More information on this criterion can be found in the protocol.
- Known allergy/sensitivity to study drugs or their formulations. A history of sulfa allergy is not an exclusion.
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with the study.
- Certain abnormal laboratory results. More information on this criterion can be found in the protocol.
- Pregnant or breastfeeding
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：RAL + DRV/RTV
Raltegravir (400 mg BID) plus Darunavir/Ritonavir (800 mg/100 mg QD) for 52 weeks
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400 mg tablet taken orally twice daily
其他名称：
800 mg Darunavir/100 mg Ritonavir tablet taken orally once daily
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Proportion of Participants With Virologic Failure After Initiating RAL Plus DRV/RTV at or Prior to Week 24
大体时间：From start of study treatment to week 24
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Virologic failure is defined as: at week 12, confirmed plasma HIV-1 RNA >= 1000 copies/ml or confirmed rebound from the week 4 value by >0.5 log10 copies/ml (for subjects with week 4 value <= 50 copies/ml, confirmed rebound to >50 copies/ml); at week 24 or later, confirmed value > 50 copies/ml.
Viral load confirmation was scheduled 7-35 days after initial virologic failure.
The proportion was estimated using Kaplan-Meier method.
An adaptation of Greenwood's variance estimate was used in constructing the confidence interval.
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From start of study treatment to week 24
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Proportion of Participants With Virologic Failure or Off Study Treatment Regimen or Death at or Prior to Week 24
大体时间：From start of study treatment to Week 24
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The proportion of participants with virologic failure (see primary outcome measure for definition) and/or premature treatment discontinuation/modification and/or death was estimated using Kaplan-Meier method.
An adaptation of Greenwood's variance estimate was used in constructing the confidence interval.
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From start of study treatment to Week 24
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Change in Plasma HIV-1 RNA From Baseline to Week 1
大体时间：Baseline and week 1
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Results report the week 1 change from baseline (week 1 - baseline) in HIV-1 RNA.
Baseline HIV-1 RNA was computed as the mean of the log10 HIV-1 RNA values at pre-entry and study entry.
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Baseline and week 1
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Proportion of Participants With Plasma HIV-1 RNA < 50 Copies/ml or <200 Copies/ml at Week 24
大体时间：From start of study treatment to week 24
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Results report the percentage of participants with plasma HIV-1 RNA < 50 copies/ml or <200 copies/ml at week 24.
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From start of study treatment to week 24
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Proportion of Participants With Plasma HIV-1 RNA <50 Copies/ml or <200 Copies/ml at Week 48
大体时间：From start of study treatment to week 48
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Results report the percentage of participants with plasma HIV-1 RNA <50 copies/ml or <200 copies/ml at week 48.
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From start of study treatment to week 48
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Proportion of Participants Who Experienced Signs/Symptoms or Laboratory Toxicities Grade 3 or Higher, or of Any Grade Which Led to a Permanent Change or Discontinuation of Study Treatment
大体时间：From start of study treatment to week 52
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Signs, symptoms and laboratory values were graded according to the Division of AIDS Adverse Event Grading System.
Results report the percentage of participants who had grade 3 or higher events, or events of any grade which led to a permanent change or discontinuation of study treatment, which occurred any time from start of treatment to end of treatment.
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From start of study treatment to week 52
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Number of Participants With Pretreatment Drug Resistance
大体时间：At screening
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Results report the number of participants who had resistance to non-nucleoside reverse transciptase inhibitors (NNRTI), nucleoside reverse transciptase inhibitors (NRTI) and protease inbitors (PI) based on genotypic resistance testing done prior to participant's entry into the study.
Participants are classified into one (and only one category) based on the maximum number of drug class resistance seen for the participant.
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At screening
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Number of Participants With Integrase Drug Resistance at Virologic Failure
大体时间：From 12 weeks after starting study treatment to week 52
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Results report the number of participants who had integrase resistance mutation(s) detected at the time of virologic failure.
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From 12 weeks after starting study treatment to week 52
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Number of Participants With Protease Drug Resistance at Virologic Failure
大体时间：From 12 weeks after starting study treatment to week 52
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Results report the number of participants who had protease resistance mutation(s) detected at the time of virologic failure.
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From 12 weeks after starting study treatment to week 52
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Number of Participants With Perfect Overall Adherence by Self Report
大体时间：From one week after starting study treatment to week 52
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At each study visit, adherence was measured in terms of the number of missed doses each participant had over a 4-day recall for each drug.
Adherence for all study visit weeks were combined for an overall measure of adherence.
Participants who had zero missed doses on all weeks in all drugs while on study were classified as having an overall "perfect" adherence.
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From one week after starting study treatment to week 52
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Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 24
大体时间：From start of study treatment through week 24
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Results report the week 24 change from week 0 (week 24 - week 0) fasting total cholesterol, high-density lipoprotein and triglyceride.
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From start of study treatment through week 24
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Change in Fasting Low-density Lipoprotein at Week 24
大体时间：From start of study treatment through week 24
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Results report the week 24 change from week 0 (week 24 - week 0) fasting low-density lipoprotein (LDL).
For participants whose calculated fasting LDL and direct fasting LDL were both reported, only the calculated fasting LDL was used.
Direct fasting LDL was reported when the participant had high fasting triglyceride.
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From start of study treatment through week 24
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Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 48
大体时间：From start of study treatment through week 48
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Results report the week 48 change from week 0 (week 48 - week 0) fasting total cholesterol, high-density lipoprotein and triglyceride.
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From start of study treatment through week 48
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Change in Fasting Low-density Lipoprotein at Week 48
大体时间：From start of study treatment through week 48
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Results report the week 48 change from week 0 (week 48 - week 0) fasting low-density lipoprotein (LDL).
For participants whose calculated fasting LDL and direct fasting LDL were both reported, only the calculated fasting LDL was used.
Direct fasting LDL was reported when the participant had high fasting triglyceride.
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From start of study treatment through week 48
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Change in CD4 Count at Week 48
大体时间：From start of study treatment through week 48
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Results report the week 48 change from baseline (week 48 - baseline) in CD4 count.
Baseline CD4 count was computed as the mean of CD4 count values at pre-entry and study entry.
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From start of study treatment through week 48
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Plasma Trough Concentration of Raltegravir
大体时间：From start of study treatment to week 52
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Plasma trough concentrations (ng/ml) of Raltegravir (RAL) below the detection limit (10 ng/ml) were replaced by half the corresponding lower limit of quantitation.
Geometric mean of trough concentrations obtained within the prescribed trough time (within 9-15 hours after the last RAL dose) was computed for each participant.
For participants who experienced virologic failure (see primary outcome measure definition), only those concentrations on or before virologic failure confirmation were used in the geometric mean computation.
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From start of study treatment to week 52
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Plasma Trough Concentration of Darunavir
大体时间：From start of study treatment to week 52
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Plasma trough concentrations (ng/ml) of Darunavir (DRV) below the detection limit (50 ng/ml) were replaced by half the corresponding lower limit of quantitation.
Geometric mean of trough concentrations obtained within the prescribed trough time (within 20-28 hours after the last DRV dose) was computed for each participant.
For participants who experienced virologic failure (see primary outcome measure definition), only those concentrations on or before virologic failure confirmation were used in the geometric mean computation.
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From start of study treatment to week 52
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Capetti AF, Piconi S, Landonio S, Rizzardini G, Perno CF. Is dual therapy with raltegravir and protease inhibitors a feasible option in rescue strategy in HIV-1 infection? J Acquir Immune Defic Syndr. 2009 Feb 1;50(2):233-4. doi: 10.1097/QAI.0b013e31818c7e8e. No abstract available.
- Long MC, King JR, Acosta EP. Pharmacologic aspects of new antiretroviral drugs. Curr HIV/AIDS Rep. 2009 Feb;6(1):43-50. doi: 10.1007/s11904-009-0007-y.
- Vermeir M, Lachau-Durand S, Mannens G, Cuyckens F, van Hoof B, Raoof A. Absorption, metabolism, and excretion of darunavir, a new protease inhibitor, administered alone and with low-dose ritonavir in healthy subjects. Drug Metab Dispos. 2009 Apr;37(4):809-20. doi: 10.1124/dmd.108.024109. Epub 2009 Jan 8.
- Taiwo B, Zheng L, Gallien S, Matining RM, Kuritzkes DR, Wilson CC, Berzins BI, Acosta EP, Bastow B, Kim PS, Eron JJ Jr; ACTG A5262 Team. Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262). AIDS. 2011 Nov 13;25(17):2113-22. doi: 10.1097/QAD.0b013e32834bbaa9.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2009年4月1日
初级完成 (实际的)
2010年2月1日
研究完成 (实际的)
2010年9月1日
研究注册日期
首次提交
2009年1月26日
首先提交符合 QC 标准的
2009年1月27日
首次发布 (估计)
2009年1月28日
研究记录更新
最后更新发布 (实际的)
2018年11月8日
上次提交的符合 QC 标准的更新
2018年10月11日
最后验证
2018年10月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.