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

NCT00677833 | Completed Phase 2 Results DMC

• 1 other identifier: A0661157
• Study Type: interventional
• Target: 361
• Locations: 5 countries
• Sites: 7

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.

Conditions

Malaria, Falciparum

Keywords

P. Falciparum Malaria; drug treatment; clinical trial

Outcome Measures

Primary Outcomes (2)

• 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

  ACPR (PCR-corrected) was defined as asexual Plasmodium falciparum (P.falciparum) parasitologic clearance at Day 28 irrespective of axillary, oral, rectal, or tympanic temperature, without previously meeting the criteria of Early Treatment Failure (ETF) (see measure description in secondary outcome measures 7 and 8) or PCR-corrected Late Treatment Failure (LTF) (which includes PCR-corrected Late Clinical Failures \[LCF\] - see measure description in secondary outcome measure 9 and 10, and PCR-corrected Late Parasitologic Failures (LPF)- see measure description in secondary outcome measure 11 and 12). PCR-corrected refers to the use of molecular testing to differentiate recrudescence from reinfection in the context of an efficacy evaluation.

  Day 28

• Percentage of Participants With PCR-corrected ACPR at Day 28 in Per-Protocol (PP) Population

  ACPR (PCR-corrected) was defined as asexual P.falciparum parasitologic clearance at Day 28 irrespective of axillary, oral, rectal, or tympanic temperature, without previously meeting the criteria of ETF (see measure description in secondary outcome measures 7 and 8) or PCR-corrected LTF (which includes PCR-corrected LCF - see measure description in secondary outcome measure 9 and 10, and PCR-corrected LPF - see measure description in secondary outcome measure 11 and 12). PCR-corrected refers to the use of molecular testing to differentiate recrudescence from reinfection in the context of an efficacy evaluation.

  Day 28

Secondary Outcomes (19)

• Percentage of Participants With PCR-corrected ACPR in the mITT Population

  Days 7, 14, 21, 35, 42

• Percentage of Participants With PCR-corrected ACPR in PP Population

  Days 7, 14, 21, 35, 42

• Percentage of Participants With PCR-uncorrected ACPR in the mITT Population

  Days 7, 14, 21, 28, 35, 42

• Percentage of Participants With PCR-uncorrected ACPR in PP Population

  Days 7, 14, 21, 28, 35, 42

• Percentage of Participants With Early Treatment Failure (ETF) in the mITT Population (PCR-corrected)

  Day 0 up to Day 3

Study Arms (2)

1

EXPERIMENTAL

Drug: Azithromycin plus Chloroquine

2

EXPERIMENTAL

Drug: Artemether-lumefantrine

Interventions

Azithromycin plus Chloroquine DRUG

Combination of Azithromycin plus Chloroquine Azithromycin (\~30 mg/kg) + chloroquine (\~10mg base /kg) combination tablet(s) on weight basis, once daily for 3 days (Days 0,1,2) or Artemether-lumefantrine tablet(s) based on weight and labeling for 3 days (Days 0, 1, 2)

1

Artemether-lumefantrine DRUG

Artemether-lumefantrine tablet(s) based on weight and labeling for 3 days (Days 0, 1, 2)

2

Eligibility Criteria

• Age: 6 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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;

Sponsors & Collaborators

• Pfizer: lead

Study Sites (7)

Pfizer Investigational Site

Nouna, Burkina Faso

Location

Pfizer Investigational Site

Ouagadougou, Burkina Faso

Location

Pfizer Investigational Site

Abidjan, Côte d’Ivoire

Location

Pfizer Investigational Site

Navrongo, Ghana

Location

Pfizer Investigational Site

Kisumu, 40100, Kenya

Location

Pfizer Investigational Site

Bamako, West Africa, Mali

Location

Pfizer Investigational Site

Sikasso, West Africa, Mali

Location

Related Publications (1)

• 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.

  PMID: 25881046 DERIVED

Related Links

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

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Azithromycin; Chloroquine; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

Cohort 1 was a screening cohort, meant for safety evaluation, but not included in the efficacy assessments.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2008
• First Posted: May 15, 2008
• Study Start: June 1, 2008
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: June 26, 2014
• Results First Posted: June 26, 2014

Record last verified: 2014-05

Locations

KE (1); BU (2); GH (1); CÔ (1); MA (2)