- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT01632891
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
연구 개요
상태
상세 설명
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.
연구 유형
등록 (실제)
단계
- 2 단계
- 1단계
연락처 및 위치
연구 장소
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Blantyre, 말라위
- College of Med. JHU CRS (30301)
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Kampala, 우간다
- Joint Clinical Research Centre (JCRC) (12401)
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Eldoret, 케냐, 30100
- AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)
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Kericho, 케냐, 20200
- Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501)
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Kisumu, 케냐, 40100
- Kisumu Crs (31460)
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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.
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 |
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실험적: 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.
다른 이름들:
Participants received one 200 mg/300 mg tablet of Emtricitabine/tenofovir disoproxil fumarate orally once daily.
다른 이름들:
Participants received one 600 mg tablet of efavirenz orally once daily.
다른 이름들:
If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.
다른 이름들:
Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily.
다른 이름들:
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실험적: 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.
다른 이름들:
Participants received one 600 mg tablet of efavirenz orally once daily.
다른 이름들:
If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.
다른 이름들:
Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Proportion of Participants With Plasmodium Falciparum (Pf) Subclinical Parasitemia (SCP) Clearance
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Time to First Pf SCP Clearance
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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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공동 작업자 및 조사자
수사관
- 연구 의자: Johnstone Kumwenda, FRCP, College of Medicine-Johns Hopkins Project
- 연구 의자: Douglas Shaffer, MD, MHS, Kenya Medical Research Institute/Walter Reed Project
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
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
- 병리학적 과정
- 감염
- 전신 염증 반응 증후군
- 염증
- 부패
- 기생충 질병
- 기생충혈증
- 약리작용의 분자기전
- 항감염제
- 항바이러스제
- 역전사 효소 억제제
- 핵산 합성 억제제
- 효소 억제제
- 항HIV제
- 항레트로바이러스제
- 프로테아제 억제제
- 시토크롬 P-450 CYP3A 억제제
- 시토크롬 P-450 효소 억제제
- 시토크롬 P-450 효소 유도제
- 항원충제
- 구충제
- 시토크롬 P-450 CYP3A 유도제
- HIV 프로테아제 억제제
- 바이러스성 프로테아제 억제제
- 항말라리아제
- 엽산 길항제
- 사이토크롬 P-450 CYP2B6 유도제
- 시토크롬 P-450 CYP2C9 억제제
- 항이상운동증제
- 항감염제, 비뇨기
- 신장 작용제
- 시토크롬 P-450 CYP2C19 억제제
- 시토크롬 P-450 CYP2C8 억제제
- 테노포비어
- 엠트리시타빈
- 네비라핀
- 리토나비어
- 로피나비르
- 엠트리시타빈, 테노포비르 디소프록실 푸마르산염 복합제
- 에파비렌즈
- 트리메토프림
- 설파메톡사졸
기타 연구 ID 번호
- ACTG A5297
- 1U01AI068636 (미국 NIH 보조금/계약)
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
미국에서 제조되어 미국에서 수출되는 제품
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