Azithromycin Plus Chloroquine Versus Artemether-Lumefantrine For The Treatment Of Uncomplicated P. Falciparum Malaria In Children In Africa

Condition(s) targeted: Malaria, Falciparum

Intervention: Azithromycin plus Chloroquine (Drug); Chloroquine (Drug); Artemether-lumefantrine (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: Pfizer

Official(s) and/or principal investigator(s):
Pfizer CT.gov Call Center, Study Director, Affiliation: Pfizer

Overall contact:
Pfizer CT.gov Call Center, Phone: 1-800-718-1021

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.

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 design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

The primary endpoint is based on the proportion of subjects with Adequate Clinical & Parasitologic Response (ACPR; PCR corrected, determining recrudescence or reinfection) at Day 28 .

The primary objective is to confirm azithromycin plus chloroquine vs. artemether-lumefantrine for the treatment of symptomatic, uncomplicated malaria due to P. falciparum in children in African countries.

Secondary outcome:

% PfCRT in true failures.

Secondary objectives include the assessment of the safety, efficacy, and tolerability of all treatment regimens.

% of subjects with Early Treatment Failure (ETF), Late Clinical Failure (LCF, PCR corrected), Late Parasitologic Failure (LPF, PCR corrected)

Asexual P. falciparum parasite clearance rate at 7, 14, 21, 35 and 42 days; Asexual P. falciparum parasite clearance time;

P. falciparum gametocyte absence rate at 7, 14, 21, 28, 35 and 42 days;

Fever clearance time;

Hematologic recovery among subjects anemic at nadir from Day 0, Day 1, Day 2, or Day 3;

Safety of all study regimens;

Time to recurrence of parasitemia; Recurrent parasitemia vs. PfCRT status at Baseline;

Minimum age: 6 Months. Maximum age: 12 Years. Gender(s): Both.

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;

- Inability to drink or breastfeed;

- Unable to sit or stand as appropriate for age;

- 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.

Pfizer CT.gov Call Center, Phone: 1-800-718-1021

Pfizer Investigational Site, Nouna, Burkina Faso; Recruiting

Pfizer Investigational Site, Ouagadougou, Burkina Faso; Active, not recruiting

Pfizer Investigational Site, Ouagadougou 01, Burkina Faso; Active, not recruiting

Pfizer Investigational Site, Abidjan 13, Côte D'Ivoire; Recruiting

Pfizer Investigational Site, Navrongo, Ghana; Recruiting

Pfizer Investigational Site, Kisumu 40100, Kenya; Active, not recruiting

Pfizer Investigational Site, Ndola, Zambia; Not yet recruiting

Pfizer Investigational Site, Bamako, West Africa, Mali; Recruiting

Pfizer Investigational Site, Sikasso, West Africa, Mali; Recruiting

To obtain contact information for a study center near you, click here.

Starting date: June 2008
Ending date: March 2010
Last updated: October 8, 2009