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
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
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Kampala、ウガンダ
- Joint Clinical Research Centre (JCRC) (12401)
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Eldoret、ケニア、30100
- AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)
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Kericho、ケニア、20200
- Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501)
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Kisumu、ケニア、40100
- Kisumu Crs (31460)
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Blantyre、マラウイ
- College of Med. JHU CRS (30301)
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的: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.
他の名前:
Participants received one 200 mg/300 mg tablet of Emtricitabine/tenofovir disoproxil fumarate orally once daily.
他の名前:
Participants received one 600 mg tablet of efavirenz orally once daily.
他の名前:
If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.
他の名前:
Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily.
他の名前:
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実験的: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.
他の名前:
Participants received one 600 mg tablet of efavirenz orally once daily.
他の名前:
If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.
他の名前:
Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily.
他の名前:
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Proportion of Participants With Plasmodium Falciparum (Pf) Subclinical Parasitemia (SCP) Clearance
時間枠: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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Time to First Pf SCP Clearance
時間枠: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)
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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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協力者と研究者
捜査官
- スタディチェア:Johnstone Kumwenda, FRCP、College of Medicine-Johns Hopkins Project
- スタディチェア:Douglas Shaffer, MD, MHS、Kenya Medical Research Institute/Walter Reed Project
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
- 病理学的プロセス
- 感染症
- 全身性炎症反応症候群
- 炎症
- 敗血症
- 寄生虫症
- 寄生虫血症
- 薬理作用の分子機構
- 抗感染剤
- 抗ウイルス剤
- 逆転写酵素阻害剤
- 核酸合成阻害剤
- 酵素阻害剤
- 抗HIV薬
- 抗レトロウイルス剤
- プロテアーゼ阻害剤
- シトクロム P-450 CYP3A 阻害剤
- シトクロム P-450 酵素阻害剤
- シトクロム P-450 酵素誘導剤
- 抗原虫剤
- 駆虫剤
- シトクロム P-450 CYP3A インデューサー
- HIVプロテアーゼ阻害剤
- ウイルスプロテアーゼ阻害剤
- 抗マラリア薬
- 葉酸拮抗薬
- シトクロム P-450 CYP2B6 インデューサー
- シトクロム P-450 CYP2C9 阻害剤
- 抗ジスキネジア剤
- 抗感染薬、尿
- 腎剤
- シトクロム P-450 CYP2C19 阻害剤
- シトクロム P-450 CYP2C8 阻害剤
- テノホビル
- エムトリシタビン
- ネビラピン
- リトナビル
- ロピナビル
- エムトリシタビン、テノホビル ジソプロキシル フマル酸塩の配合剤
- エファビレンツ
- トリメトプリム
- スルファメトキサゾール
その他の研究ID番号
- ACTG A5297
- 1U01AI068636 (米国 NIH グラント/契約)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
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