- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus 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
Tutkimuksen yleiskatsaus
Tila
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Ilmoittautuminen (Todellinen)
Vaihe
- Vaihe 2
- Vaihe 1
Yhteystiedot ja paikat
Opiskelupaikat
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Eldoret, Kenia, 30100
- AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)
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Kericho, Kenia, 20200
- Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501)
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Kisumu, Kenia, 40100
- Kisumu Crs (31460)
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Blantyre, Malawi
- College of Med. JHU CRS (30301)
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Kampala, Uganda
- Joint Clinical Research Centre (JCRC) (12401)
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: 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.
Muut nimet:
Participants received one 200 mg/300 mg tablet of Emtricitabine/tenofovir disoproxil fumarate orally once daily.
Muut nimet:
Participants received one 600 mg tablet of efavirenz orally once daily.
Muut nimet:
If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.
Muut nimet:
Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily.
Muut nimet:
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Kokeellinen: 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.
Muut nimet:
Participants received one 600 mg tablet of efavirenz orally once daily.
Muut nimet:
If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.
Muut nimet:
Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily.
Muut nimet:
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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Proportion of Participants With Plasmodium Falciparum (Pf) Subclinical Parasitemia (SCP) Clearance
Aikaikkuna: 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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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Time to First Pf SCP Clearance
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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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Yhteistyökumppanit ja tutkijat
Sponsori
Yhteistyökumppanit
Tutkijat
- Opintojen puheenjohtaja: Johnstone Kumwenda, FRCP, College of Medicine-Johns Hopkins Project
- Opintojen puheenjohtaja: Douglas Shaffer, MD, MHS, Kenya Medical Research Institute/Walter Reed Project
Julkaisuja ja hyödyllisiä linkkejä
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Arvio)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
- Patologiset prosessit
- Infektiot
- Systeeminen tulehdusvasteen oireyhtymä
- Tulehdus
- Sepsis
- Parasiittiset sairaudet
- Parasitemia
- Farmakologisen vaikutuksen molekyylimekanismit
- Infektiota estävät aineet
- Viruksenvastaiset aineet
- Käänteiskopioijaentsyymin estäjät
- Nukleiinihapposynteesin estäjät
- Entsyymin estäjät
- HIV-vastaiset aineet
- Antiretroviraaliset aineet
- Proteaasin estäjät
- Sytokromi P-450 CYP3A:n estäjät
- Sytokromi P-450 -entsyymin estäjät
- Sytokromi P-450 entsyymin indusoijat
- Alkueläinten vastaiset aineet
- Antiparasiittiset aineet
- Sytokromi P-450 CYP3A:n indusoijat
- HIV-proteaasin estäjät
- Viruksen proteaasin estäjät
- Malarialääkkeet
- Foolihappoantagonistit
- Sytokromi P-450 CYP2B6:n indusoijat
- Sytokromi P-450 CYP2C9:n estäjät
- Dyskinesian vastaiset aineet
- Infektiota estävät aineet, virtsatie
- Munuaisten aineet
- Sytokromi P-450 CYP2C19:n estäjät
- Sytokromi P-450 CYP2C8:n estäjät
- Tenofoviiri
- Emtrisitabiini
- Nevirapiini
- Ritonaviiri
- Lopinaviiri
- Emtrisitabiini, tenofoviiridisoproksiilifumaraattiyhdistelmä
- Efavirents
- Trimetopriimi
- Sulfametoksatsoli
Muut tutkimustunnusnumerot
- ACTG A5297
- 1U01AI068636 (Yhdysvaltain NIH-apuraha/sopimus)
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
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Yhdysvalloissa valmistettu ja sieltä viety tuote
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