Clinical trial NCT00677833: Azithromycin Plus Chloroquine Versus Artemether-Lumefantrine For The Treatment Of Uncomplicated P. Falciparum Malaria In Children In Africa
Official title: Phase 2/3, Open-Label, Comparative Trial Of Azithromycin Plus Chloroquine Versus Artemether-Lumefantrine For The Treatment Of Uncomplicated Plasmodium Falciparum Malaria In Children In Africa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Malaria, Falciparum
Keywords: P. Falciparum Malaria
drug treatment
clinical trial
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-05-15
Enrollment: 361
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to confirm the hypothesis that azithromycin used in combination with chloroquine is non-inferior to artemether- Lumefantrine for the treatment of symptomatic, uncomplicated malaria due to P. falciparum in children in African countries.


Eligibility criteria: Inclusion Criteria:

* Girls and boys ≥5 years to ≤12 years (Cohort 1); and ≥6 to ≤59 months of age (Cohort 2) with uncomplicated, symptomatic malaria as indicated by the presence of the following:
* Blood smears positive for monoinfection with P. falciparum and asexual parasitemia between 1000 -100,000 parasites/µL;
* Documented fever (38.0°C/100.4°F rectal or tympanic; 37.2°C/99.0°F axillary or 37.5°C/99.5°F oral) or history of fever (as reported by the legally acceptable representative) within the prior 24 hours;
* Appropriate for outpatient treatment;
* Blood glucose ≥60 mg/dL;
* Hemoglobin ≥6 g/dl or hematocrit ≥18% without signs of anemia-induced Congestive Heart Failure (CHF);
* Negative urine pregnancy test for females ≥10 years of age (and of child bearing potential)

Exclusion Criteria:

* Peripheral blood smear positive for mixed infection with multiple Plasmodium spp.
* Severe or complicated malaria including subjects with any of the following:
* Impaired consciousness (eg, obtundation, unarousable coma), seizures or abnormal neurologic exam suggestive of severe or complicated malaria;
* Known hemoglobinuria;
* Jaundice;
* Respiratory distress;
* Persistent vomiting;
* Gross hematuria, as reported by the subject's legally acceptable representative;
* Recent history of convulsions;
* Inability to drink or breastfeed;
* Unable to sit or stand as appropriate for age;
* Known pregnancy or breast-feeding or positive urine pregnancy test (females ≥10 years of age and of child bearing potential);
* History of allergy to or hypersensitivity to azithromycin, any macrolide, chloroquine, artemether, any artemisinin derivative, lumefantrine;
* Any contraindication to any study drug including AZ, CQ and AL;
* History of treatment with any antimalarial drug (such as halofantrine, chloroquine, quinine, mefloquine, Malarone, SP, artemisinin compounds) or antibacterial with known antimalarial activity (macrolides, doxycycline, clindamycin) within 2 weeks prior to enrollment of a subject (and/or of the mother of a subject who is being breastfed) into the study;
* Known or suspected cardiovascular, hepatic or renal abnormality that in the opinion of the investigator would place the subject at increased risk to participate in the study.

Primary outcomes:
measure: Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitologic Response (ACPR) at Day 28 in the Modified Intent-to-treat (mITT) Population
timeFrame: Day 28
measure: Percentage of Participants With PCR-corrected ACPR at Day 28 in Per-Protocol (PP) Population
timeFrame: Day 28
Secondary outcomes:
measure: Percentage of Participants With PCR-corrected ACPR in the mITT Population
timeFrame: Days 7, 14, 21, 35, 42
measure: Percentage of Participants With PCR-corrected ACPR in PP Population
timeFrame: Days 7, 14, 21, 35, 42
measure: Percentage of Participants With PCR-uncorrected ACPR in the mITT Population
timeFrame: Days 7, 14, 21, 28, 35, 42
measure: Percentage of Participants With PCR-uncorrected ACPR in PP Population
timeFrame: Days 7, 14, 21, 28, 35, 42
measure: Percentage of Participants With Early Treatment Failure (ETF) in the mITT Population (PCR-corrected)
timeFrame: Day 0 up to Day 3
measure: Percentage of Participants With ETF in PP Population (PCR-corrected)
timeFrame: Day 0 up to Day 3
measure: Percentage of Participants With Late Clinical Failure (LCF) in the mITT Population (PCR-corrected)
timeFrame: Days 7, 14, 21, 28, 35, 42
measure: Percentage of Participants With LCF in PP Population (PCR-corrected)
timeFrame: Days 7, 14, 21, 28, 35, 42
measure: Percentage of Participants With Late Parasitologic Failure (LPF) in the mITT Population (PCR-corrected)
timeFrame: Days 7, 14, 21, 28, 35, 42
measure: Percentage of Participants With LPF in PP Population (PCR-corrected)
timeFrame: Days 7, 14, 21, 28, 35, 42
measure: Percentage of Participants With Asexual Parasitologic Response (PCR-corrected)
timeFrame: Day 7, 14, 21, 28, 35, 42
measure: Percentage of Participants With Gametocytologic Response
timeFrame: Days 7, 14, 21, 28, 35, 42
measure: Fever Clearance Time
timeFrame: Baseline to Day 42
measure: Asexual Plasmodium Falciparum Parasite Clearance Time
timeFrame: Baseline to Day 42
measure: Nadir Hemoglobin Level
timeFrame: Day 0 through Day 3
measure: Change From Nadir Hemoglobin Level at Days 14, 28, and 42
timeFrame: Day 14, 28, 42
measure: Time to Recurrence of Parasitemia
timeFrame: Baseline (Day 0) to Day 42
measure: Number of Participants With Recurrent Parasitemia Versus Baseline Plasmodium Falciparum Chloroquine Resistance Transporter (PfCRT) Status
timeFrame: Baseline to Day 42
measure: Percentage of Participants With PfCRT in True Failures
timeFrame: Baseline to Day 42
Other outcomes:
Locations:
city: Nouna
country: Burkina Faso
facility: Pfizer Investigational Site
city: Ouagadougou 01
country: Burkina Faso
facility: Pfizer Investigational Site
city: Ouagadougou
country: Burkina Faso
facility: Pfizer Investigational Site
city: Abidjan 13
country: Côte D'Ivoire
facility: Pfizer Investigational Site
city: Navrongo
country: Ghana
facility: Pfizer Investigational Site
city: Kisumu
country: Kenya
facility: Pfizer Investigational Site
city: Bamako
country: Mali
facility: Pfizer Investigational Site
state: West Africa
city: Sikasso
country: Mali
facility: Pfizer Investigational Site
state: West Africa
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Chandra R, Ansah P, Sagara I, Sie A, Tiono AB, Djimde AA, Zhao Q, Robbins J, Penali LK, Ogutu B. Comparison of azithromycin plus chloroquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children in Africa: a randomized, open-label study. Malar J. 2015 Mar 10;14:108. doi: 10.1186/s12936-015-0620-8.