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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase 2/3, Open-Label, Comparative Trial Of Azithromycin Plus Chloroquine Versus Artemether-Lumefantrine For The Treatment Of Uncomplicated Plasmodium Falciparum Malaria I

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.

Detailed Summary:
Sponsor: Pfizer

Current Primary Outcome:

  • 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 [ Time Frame: Day 28 ]
    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.
  • Percentage of Participants With PCR-corrected ACPR at Day 28 in Per-Protocol (PP) Population [ Time Frame: Day 28 ]
    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.


Original 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 . [ Time Frame: during the study ]
  • 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. [ Time Frame: during the study ]


Current Secondary Outcome:

  • Percentage of Participants With PCR-corrected ACPR in the mITT Population [ Time Frame: Days 7, 14, 21, 35, 42 ]
    ACPR (PCR-corrected) was defined as asexual P.falciparum parasitologic clearance on Days 7, 14, 21, 35, 42 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.
  • Percentage of Participants With PCR-corrected ACPR in PP Population [ Time Frame: Days 7, 14, 21, 35, 42 ]
    ACPR (PCR-corrected) was defined as asexual P.falciparum parasitologic clearance on Days 7, 14, 21, 35, 42 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.
  • Percentage of Participants With PCR-uncorrected ACPR in the mITT Population [ Time Frame: Days 7, 14, 21, 28, 35, 42 ]
    ACPR (PCR-uncorrected) was defined as asexual P.falciparum parasitologic clearance on Days 7, 14, 21, 28, 35, 42 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-uncorrected LTF (which includes PCR-uncorrected LCF - see measure description in secondary outcome measure 9 and 10, and PCR-uncorrected LPF - see measure description in secondary outcome measure 11 and 12). PCR-uncorrected: not adjusted for molecular testing which determined recrudescence or true failures from reinfection.
  • Percentage of Participants With PCR-uncorrected ACPR in PP Population [ Time Frame: Days 7, 14, 21, 28, 35, 42 ]
    ACPR (PCR-uncorrected) was defined as asexual P.falciparum parasitologic clearance on Days 7, 14, 21, 28, 35, 42 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-uncorrected LTF (which includes PCR-uncorrected LCF - see measure description in secondary outcome measure 9 and 10, and PCR-uncorrected LPF - see measure description in secondary outcome measure 11 and 12). PCR-uncorrected: not adjusted for molecular testing which determined recrudescence or true failures from reinfection.
  • Percentage of Participants With Early Treatment Failure (ETF) in the mITT Population (PCR-corrected) [ Time Frame: Day 0 up to Day 3 ]

    ETF defined as participants who met the following criteria:

    1. Developed signs of severe malaria or clinical deterioration that required rescue medication on Days 0, 1, 2 or 3, in the presence of P. falciparum parasitemia
    2. Last available asexual P. falciparum parasite count on Day 2 greater than the first available parasite count on Day 0 (Baseline), irrespective of axillary, oral or rectal temperature.
    3. Parasitemia (P. falciparum) on Day 3 with fever or
    4. Last available P. falciparum parasite count on Day 3 >=25% of the first available parasite count on Day 0 (Baseline).

    PCR-corrected refers to the use of molecular testing to differentiate recrudescence from reinfection in the context of an efficacy evaluation.

  • Percentage of Participants With ETF in PP Population (PCR-corrected) [ Time Frame: Day 0 up to Day 3 ]

    ETF defined as participants who met the following criteria:

    1. Developed signs of severe malaria or clinical deterioration that required rescue medication on Days 0, 1, 2 or 3, in the presence of P.falciparum parasitemia
    2. Last available asexual P.falciparum parasite count on Day 2 greater than the first available parasite count on Day 0 (Baseline), irrespective of axillary, oral or rectal temperature.
    3. Parasitemia (P.falciparum) on Day 3 with fever or
    4. Last available P.falciparum parasite count on Day 3 >=25% of the first available parasite count on Day 0 (Baseline).

    PCR-corrected refers to the use of molecular testing to differentiate recrudescence from reinfection in the context of an efficacy evaluation.

  • Percentage of Participants With Late Clinical Failure (LCF) in the mITT Populat

    Original Secondary Outcome:

    • Asexual P. falciparum parasite clearance rate at 7, 14, 21, 35 and 42 days; Asexual P. falciparum parasite clearance time; [ Time Frame: during the study ]
    • P. falciparum gametocyte absence rate at 7, 14, 21, 28, 35 and 42 days; [ Time Frame: during the study ]
    • Fever clearance time; [ Time Frame: during the study ]
    • Hematologic recovery among subjects anemic at nadir from Day 0, Day 1, Day 2, or Day 3; [ Time Frame: during the study ]
    • Safety of all study regimens; [ Time Frame: during the study ]
    • Time to recurrence of parasitemia; Recurrent parasitemia vs. PfCRT status at Baseline; [ Time Frame: during the study ]
    • % PfCRT in true failures. [ Time Frame: during the study ]
    • Secondary objectives include the assessment of the safety, efficacy, and tolerability of all treatment regimens. [ Time Frame: during the study ]
    • % of subjects with Early Treatment Failure (ETF), Late Clinical Failure (LCF, PCR corrected), Late Parasitologic Failure (LPF, PCR corrected) [ Time Frame: during the study ]


    Information By: Pfizer

    Dates:
    Date Received: May 12, 2008
    Date Started: June 2008
    Date Completion:
    Last Updated: May 27, 2014
    Last Verified: May 2014