- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg 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
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
-
Eldoret, Kenya, 30100
- AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)
-
Kericho, Kenya, 20200
- Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501)
-
Kisumu, Kenya, 40100
- Kisumu Crs (31460)
-
-
-
-
-
Blantyre, Malawi
- College of Med. JHU CRS (30301)
-
-
-
-
-
Kampala, Uganda
- Joint Clinical Research Centre (JCRC) (12401)
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Eksperimentel: 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.
|
Participants received two 200 mg/50 mg tablets of lopinavir/ritonavir orally twice daily.
Andre navne:
Participants received one 200 mg/300 mg tablet of Emtricitabine/tenofovir disoproxil fumarate orally once daily.
Andre navne:
Participants received one 600 mg tablet of efavirenz orally once daily.
Andre navne:
If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.
Andre navne:
Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily.
Andre navne:
|
Eksperimentel: 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.
|
Participants received one 200 mg/300 mg tablet of Emtricitabine/tenofovir disoproxil fumarate orally once daily.
Andre navne:
Participants received one 600 mg tablet of efavirenz orally once daily.
Andre navne:
If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.
Andre navne:
Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily.
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Proportion of Participants With Plasmodium Falciparum (Pf) Subclinical Parasitemia (SCP) Clearance
Tidsramme: Day 15 (3 samples collected, separated by at least 5 hours and all three collected within 24-hours)
|
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)
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Time to First Pf SCP Clearance
Tidsramme: From study entry up to day 30
|
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.
|
From study entry up to day 30
|
Log10(Pf Parasite Density)
Tidsramme: Entry, days 3, 6, 9, 12, 15, 20, 25, 30
|
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.
|
Entry, days 3, 6, 9, 12, 15, 20, 25, 30
|
Change in log10(Pf Parasite Density) From Entry to Day 30
Tidsramme: Entry, Day 30
|
Change is evaluated as log10(Pf parasite density) at day 30 minus log10(Pf parasite density) at entry. Change is evaluated in four groups:
|
Entry, Day 30
|
Number of Participants With Uncomplicated Clinical Malaria
Tidsramme: From study entry to day 30
|
Uncomplicated clinical malaria is defined as the presence of non-severe fever/symptoms and parasitemia without organ complication.
|
From study entry to day 30
|
Number of Participants With Detectable Pf Gametocyte Density
Tidsramme: Entry, days 3, 6, 9, 12, 15, 20, 25, 30
|
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.
|
Entry, days 3, 6, 9, 12, 15, 20, 25, 30
|
Change in log10(Pf Gametocyte Density) From Entry to Day 30
Tidsramme: Entry, Day 30
|
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
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Studiestol: Johnstone Kumwenda, FRCP, College of Medicine-Johns Hopkins Project
- Studiestol: Douglas Shaffer, MD, MHS, Kenya Medical Research Institute/Walter Reed Project
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Patologiske processer
- Infektioner
- Systemisk inflammatorisk responssyndrom
- Betændelse
- Sepsis
- Parasitiske sygdomme
- Parasitæmi
- Molekylære mekanismer for farmakologisk virkning
- Anti-infektionsmidler
- Antivirale midler
- Reverse transkriptasehæmmere
- Nukleinsyresyntesehæmmere
- Enzymhæmmere
- Anti-HIV-midler
- Anti-retrovirale midler
- Proteasehæmmere
- Cytokrom P-450 CYP3A-hæmmere
- Cytokrom P-450 enzymhæmmere
- Cytokrom P-450 enzyminducere
- Antiprotozoale midler
- Antiparasitære midler
- Cytokrom P-450 CYP3A inducere
- HIV-proteasehæmmere
- Virale proteasehæmmere
- Antimalariamidler
- Folinsyreantagonister
- Cytokrom P-450 CYP2B6 inducere
- Cytokrom P-450 CYP2C9-hæmmere
- Midler mod dyskinesi
- Anti-infektionsmidler, urinveje
- Nyremidler
- Cytokrom P-450 CYP2C19-hæmmere
- Cytokrom P-450 CYP2C8-hæmmere
- Tenofovir
- Emtricitabin
- Nevirapin
- Ritonavir
- Lopinavir
- Emtricitabin, Tenofovir Disoproxil Fumarate Lægemiddelkombination
- Efavirenz
- Trimethoprim
- Sulfamethoxazol
Andre undersøgelses-id-numre
- ACTG A5297
- 1U01AI068636 (U.S. NIH-bevilling/kontrakt)
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
produkt fremstillet i og eksporteret fra U.S.A.
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
Kliniske forsøg med HIV-1 infektion
-
Helios SaludViiV HealthcareUkendtHiv | HIV-1-infektionArgentina
-
ANRS, Emerging Infectious DiseasesInstitut National de la Santé Et de la Recherche Médicale, France; University... og andre samarbejdspartnereAfsluttetHIV-1Burkina Faso, Zambia
-
Hospital Universitari Vall d'Hebron Research InstituteGilead SciencesAfsluttet
-
Hospital Universitari Vall d'Hebron Research InstituteUniversity Hospital, Ghent; IrsiCaixaAfsluttet
-
Gilead SciencesAfsluttet
-
University of AarhusAarhus University Hospital Skejby; Bandim Health Project; Abbott; Ministry...Afsluttet
-
Tibotec Pharmaceuticals, IrelandAfsluttetHIV-1Forenede Stater, Frankrig, Spanien, Portugal, Canada, Det Forenede Kongerige, Sydafrika, Argentina, Brasilien, Puerto Rico, Thailand, Holland, Rumænien
-
Tibotec Pharmaceuticals, IrelandAfsluttetHIV-1Forenede Stater, Canada, Frankrig, Belgien, Tyskland, Spanien, Argentina, Chile, Panama, Brasilien, Puerto Rico, Thailand, Mexico, Australien
-
Mymetics CorporationInstitut Cochin; San Raffaele University Hospital, Italy; Kinesis Pharma... og andre samarbejdspartnereAfsluttet
-
Janssen Pharmaceutica N.V., BelgiumAfsluttetHIV-1Forenede Stater, Spanien
Kliniske forsøg med Lopinavir/ritonavir
-
Drugs for Neglected DiseasesUniversity of Cape Town; Medecins Sans Frontieres, Netherlands; UBS Optimus... og andre samarbejdspartnereAfsluttetErhvervet immundefektsyndrom | TuberkuloseSydafrika
-
Oswaldo Cruz FoundationMinistry of Health, BrazilAfsluttetHIV-infektioner | GraviditetBrasilien
-
Fundacion SEIMC-GESIDAAbbottAfsluttetHIV-infektioner | HIV-infektion | LipodystrofiSpanien
-
University College, LondonLifeArcAfsluttetCOVID-19Det Forenede Kongerige
-
Fundacion SEIMC-GESIDAAbbottAfsluttetHIV-infektioner | HIV/HCV Co-infektionSpanien
-
University of California, San DiegoAbbottAfsluttet
-
Institut National de la Santé Et de la Recherche...FUJIFILM Toyama Chemical Co., Ltd.RekrutteringSmitsom sygdom | FarmakologiFrankrig
-
Soroka University Medical CenterUkendt