Comparing PI-Based to a nNRTI-based ART for Clearance of Plasmodium Falciparum Parasitemia in HIV-Infected
An Open-Label, Proof of Concept, Randomized Trial Comparing a LPV/r-Based to an nNRTI-Based Antiretroviral Therapy Regimen for Clearance of Plasmodium Falciparum Subclinical Parasitemia in HIV-infected Adults With CD4+ Counts >200 and <500 Cells/mm^3
研究概览
地位
详细说明
A5297 was a Phase I/II, open-label, proof of concept, two-step, two-arm, randomized controlled clinical trial (RCT) to test the superiority of lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) to non-nucleoside reverse transcriptase (nNRTI)-based ART for clearance of Plasmodium falciparum (Pf) subclinical parasitemia (SCP).
The study consisted of two steps. At study Step 1 entry, participants were randomized 1:1 to either LPV/r-based ART or nNRTI-based ART for 15 days. In study Step 2, all participants received nNRTI-based ART and TMP/SMX prophylaxis for 15 days. The total study duration was 30 days.
Study visits occurred every 3 days in Step 1, and every 5 days in Step 2. At each study visit, 2 samples were taken for measurement of parasite density, except day 15 and day 30 at which 3 samples were taken.
Adverse events which occurred after randomization were also recorded. Signs/symptoms and diagnoses were evaluated at each visit, while safety labs (including Hemoglobin, hematocrit, white blood cell count (WBC), differential WBC, platelet count, and absolute neutrophil count (ANC), glucose, electrolytes (sodium, potassium, chloride, bicarbonate), total bilirubin, AST (SGOT), ALT (SGPT), albumin, alkaline phosphatase, and creatinine) were taken at day 15 and day 30, or if indicated at other study visits.
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Kampala、乌干达
- Joint Clinical Research Centre (JCRC) (12401)
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Eldoret、肯尼亚、30100
- AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)
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Kericho、肯尼亚、20200
- Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501)
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Kisumu、肯尼亚、40100
- Kisumu Crs (31460)
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Blantyre、马拉维
- College of Med. JHU CRS (30301)
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- HIV-1 infection
- CD4+ count > 200 and < 500 cells/mm^3 obtained within 30 days prior to study entry at a DAIDS-approved laboratory.
Pf SCP confirmed in a laboratory approved to conduct parasitemia microscopy. Note: Pf SCP defined as meeting all three of the following criteria within 72 hours prior to study entry:
- Microscopy confirmed parasitemia (see section 6.3.6 and the A5297 Manual of Procedures [MOPS])
- An oral temperature < 37.5°C.
The absence of Grade 2 or greater signs or symptoms thought to be related to clinical malaria including:
- headache
- malaise or fatigue
- abdominal discomfort
- muscle or joint pain
- fever
- chills
- perspiration
- anorexia
- vomiting
- other signs or symptoms thought to be related to clinical malaria
- Certain laboratory values obtained within 14 days prior to study entry, as detailed in section 4.1.4 of the protocol.
- Hepatitis B surface antigen (HBsAg) negative within 30 days prior to entry.
- Female study volunteers of reproductive potential have a negative serum or urine pregnancy test performed within 72 hours prior to entry.
- All study volunteers agree not to participate in a conception process (eg, active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) for study duration. If participating in sexual activity that could lead to pregnancy, must agree to use two reliable forms of contraceptive simultaneously while receiving protocol-specified medications. One form of contraceptive must be a barrier method if a participant receives EFV. Participants must agree to continue the use of two contraceptives for 6 months after stopping EFV and 6 weeks after stopping all other protocol-specified medications.
- Study volunteers who are not of reproductive potential are eligible without requiring the use of a contraceptive.
- Ability and willingness of participant or legal guardian/representative to provide informed consent.
- Willing and able to return to the clinic twice to three times a day for study visits.
Exclusion Criteria:
Step 1: Exclusion Criteria
- Previous history or current use of ART.
- Single dose NVP or dual therapies used for Prevention of mother-to-child transmission (PMTCT) within 2 years prior to entry.
- Use of any medication with antimalarial activity, including TMP/SMX (see list of prohibited medications in the A5297 Manual of Procedures (MOPS)), within 14 days prior to study entry.
- Confirmed or clinically suspected OIs (including but not limited to tuberculosis, clinical malaria, PCP), or other pulmonary or gastrointestinal infections for which potential participants did not complete treatment more than 30 days prior to enrollment or have signs and symptoms during screening.
- Breastfeeding.
- Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry.
- Results suggestive of active pulmonary disease from a chest x-ray performed within 30 days prior to study entry.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 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:LPV/r-based ART
Participants were prescribed to LPV/r-based antiretroviral therapy (ART) for 15 days, which includes lopinavir/ritonavir plus emtricitabine/tenofovir disoproxil fumarate; followed by an nNRTI-based ART, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30.
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Participants received two 200 mg/50 mg tablets of lopinavir/ritonavir orally twice daily.
其他名称:
Participants received one 200 mg/300 mg tablet of Emtricitabine/tenofovir disoproxil fumarate orally once daily.
其他名称:
Participants received one 600 mg tablet of efavirenz orally once daily.
其他名称:
If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.
其他名称:
Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily.
其他名称:
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实验性的:nNRTI-based ART
Participants were prescribed to nNRTI-based ART for 15 days, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, followed by an nNRTI-based ART and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30.
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Participants received one 200 mg/300 mg tablet of Emtricitabine/tenofovir disoproxil fumarate orally once daily.
其他名称:
Participants received one 600 mg tablet of efavirenz orally once daily.
其他名称:
If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.
其他名称:
Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole 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 Plasmodium Falciparum (Pf) Subclinical Parasitemia (SCP) Clearance
大体时间:Day 15 (3 samples collected, separated by at least 5 hours and all three collected within 24-hours)
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Pf SCP clearance defined by polymerase chain reaction (PCR) < 10 parasites/µL on three consecutive occasions within a 24-hour period. If a participant had missing data on day 15, they were considered as not having clearance. |
Day 15 (3 samples collected, separated by at least 5 hours and all three collected within 24-hours)
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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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Time to First Pf SCP Clearance
大体时间:From study entry up to day 30
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Time to clearance is defined by time to first measurement with PCR < 10 parasites/µL, and is evaluated as the point estimate and 95% CI for the day when 50% of participants cleared parasite.
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From study entry up to day 30
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Log10(Pf Parasite Density)
大体时间:Entry, days 3, 6, 9, 12, 15, 20, 25, 30
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Pf parasite density was determined by PCR.
If parasite density equals 0, the value is set to 0.01 before log10 transformation.
The value 0.01 was chosen based on the smallest observed parasite density value of 0.017.
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Entry, days 3, 6, 9, 12, 15, 20, 25, 30
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Change in log10(Pf Parasite Density) From Entry to Day 30
大体时间:Entry, Day 30
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Change is evaluated as log10(Pf parasite density) at day 30 minus log10(Pf parasite density) at entry. Change is evaluated in four groups:
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Entry, Day 30
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Number of Participants With Uncomplicated Clinical Malaria
大体时间:From study entry to day 30
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Uncomplicated clinical malaria is defined as the presence of non-severe fever/symptoms and parasitemia without organ complication.
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From study entry to day 30
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Number of Participants With Detectable Pf Gametocyte Density
大体时间:Entry, days 3, 6, 9, 12, 15, 20, 25, 30
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Number of participants with detectable Pf gametocyte density as determined by PCR.
Due to the large number of undetectable results, this outcome was measured as dichotomous.
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Entry, days 3, 6, 9, 12, 15, 20, 25, 30
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Change in log10(Pf Gametocyte Density) From Entry to Day 30
大体时间:Entry, Day 30
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Change in log10(Pf gametocyte density) as evaluated using a Hodges-Lehmann estimate from entry to day 30 is evaluated in two groups:
Analysis was not conducted in either group with clearance at day 15 due to the small sample size and high number of undetectable samples in both clearance groups at entry and day 30. |
Entry, Day 30
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合作者和调查者
调查人员
- 学习椅:Johnstone Kumwenda, FRCP、College of Medicine-Johns Hopkins Project
- 学习椅:Douglas Shaffer, MD, MHS、Kenya Medical Research Institute/Walter Reed Project
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
- 病理过程
- 感染
- 全身炎症反应综合征
- 炎
- 败血症
- 寄生虫病
- 寄生虫血症
- 药理作用的分子机制
- 抗感染药
- 抗病毒药物
- 逆转录酶抑制剂
- 核酸合成抑制剂
- 酶抑制剂
- 抗艾滋病药物
- 抗逆转录病毒药物
- 蛋白酶抑制剂
- 细胞色素 P-450 CYP3A 抑制剂
- 细胞色素 P-450 酶抑制剂
- 细胞色素 P-450 酶诱导剂
- 抗原虫剂
- 抗寄生虫药
- 细胞色素 P-450 CYP3A 诱导剂
- HIV 蛋白酶抑制剂
- 病毒蛋白酶抑制剂
- 抗疟药
- 叶酸拮抗剂
- 细胞色素 P-450 CYP2B6 诱导剂
- 细胞色素 P-450 CYP2C9 抑制剂
- 抗运动障碍药
- 抗感染药,泌尿
- 肾脏药物
- 细胞色素 P-450 CYP2C19 抑制剂
- 细胞色素 P-450 CYP2C8 抑制剂
- 替诺福韦
- 恩曲他滨
- 奈韦拉平
- 利托那韦
- 洛匹那韦
- 恩曲他滨、替诺福韦地索普西富马酸盐药物组合
- 依法韦仑
- 甲氧苄啶
- 磺胺甲恶唑
其他研究编号
- ACTG A5297
- 1U01AI068636 (美国 NIH 拨款/合同)
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
在美国制造并从美国出口的产品
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