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Trial record 1 of 1 for:    NCT00677833
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Azithromycin Plus Chloroquine Versus Artemether-Lumefantrine For The Treatment Of Uncomplicated P. Falciparum Malaria In Children In Africa

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ClinicalTrials.gov Identifier: NCT00677833
Recruitment Status : Completed
First Posted : May 15, 2008
Results First Posted : June 26, 2014
Last Update Posted : June 26, 2014
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE May 12, 2008
First Posted Date  ICMJE May 15, 2008
Results First Submitted Date  ICMJE May 27, 2014
Results First Posted Date  ICMJE June 26, 2014
Last Update Posted Date June 26, 2014
Study Start Date  ICMJE June 2008
Actual Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 27, 2014)
  • 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 Measures  ICMJE
 (submitted: May 12, 2008)
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2014)
  • 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 Population (PCR-corrected) [ Time Frame: Days 7, 14, 21, 28, 35, 42 ]
    LCF included participants who met any of the following criteria:
    1. Development of signs of severe malaria or clinical deterioration requiring rescue medication after Day 3 in the presence of P.falciparum parasitemia, without previously meeting any of the criteria of ETF (see measure description in secondary outcome measures 7 and 8)
    2. Presence of P.falciparum parasitemia and fever on any day from Day 4 onward, without previously meeting any of the criteria of ETF (see measure description in secondary outcome measures 7 and 8). 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 LCF in PP Population (PCR-corrected) [ Time Frame: Days 7, 14, 21, 28, 35, 42 ]
    LCF included participants who met any of the following criteria:
    1. Development of signs of severe malaria or clinical deterioration requiring rescue medication after Day 3 in the presence of P.falciparum parasitemia, without previously meeting any of the criteria of ETF (see measure description in secondary outcome measures 7 and 8)
    2. Presence of P.falciparum parasitemia and fever on any day from Day 4 onward, without previously meeting any of the criteria of ETF (see measure description in secondary outcome measures 7 and 8). 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 Parasitologic Failure (LPF) in the mITT Population (PCR-corrected) [ Time Frame: Days 7, 14, 21, 28, 35, 42 ]
    LPF: Presence of P. falciparum parasitemia in the mITT population on any day from Day 7 onward and the absence of fever without previously meeting any of the criteria of ETF (see measure description in secondary outcome measures 7 and 8) or LCF (see measure description in secondary outcome measure 9 and 10). 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 LPF in PP Population (PCR-corrected) [ Time Frame: Days 7, 14, 21, 28, 35, 42 ]
    LPF: Presence of P.falciparum parasitemia in the PP population on any day from Day 7 onward and the absence of fever without previously meeting any of the criteria of ETF (see measure description in secondary outcome measures 7 and 8) or LCF (see measure description in secondary outcome measure 9 and 10). 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 Asexual Parasitologic Response (PCR-corrected) [ Time Frame: Day 7, 14, 21, 28, 35, 42 ]
    Percentage of participants who were cleared of asexual parasites. Asexual parasite clearance - clearance of asexual P.falciparum parasitemia within 7 days of initiation of treatment without subsequent recurrence (PCR-corrected) through the day of consideration. 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 Gametocytologic Response [ Time Frame: Days 7, 14, 21, 28, 35, 42 ]
    Gametocyte response/absence/clearance: Clearance of P.falciparum gametocytemia (PCR-uncorrected) (attainment of 2 consecutive zero gametocyte counts) without subsequent recurrence through the day of consideration. PCR-uncorrected: not adjusted for molecular testing which determined recrudescence or true failures from reinfection.
  • Fever Clearance Time [ Time Frame: Baseline to Day 42 ]
    Calculated as time of first occurrence of two consecutive time points with temperature less than (<) 38.0 degrees C/100.4 degrees Fahrenheit (F) (rectal), 37.2 degrees C/99.0 degrees F (axillary), or <37.5 degrees C/99.5 degrees F (oral).
  • Asexual Plasmodium Falciparum Parasite Clearance Time [ Time Frame: Baseline to Day 42 ]
    Defined as time to first of two consecutive zero asexual P. falciparum parasite (PCR-corrected) counts, regardless of recurrence of parasitemia later. PCR-corrected refers to the use of molecular testing to differentiate recrudescence from reinfection in the context of an efficacy evaluation.
  • Nadir Hemoglobin Level [ Time Frame: Day 0 through Day 3 ]
    Nadir hemoglobin for each participant was defined as the minimum hemoglobin values obtained from Day 0 through Day 3.
  • Change From Nadir Hemoglobin Level at Days 14, 28, and 42 [ Time Frame: Day 14, 28, 42 ]
    Change from nadir = observation minus nadir. Nadir defined as the minimum value for each participant on Days 0-3.
  • Time to Recurrence of Parasitemia [ Time Frame: Baseline (Day 0) to Day 42 ]
    Time from the day of clearance to the time of recurrence of asexual P.falciparum parasitemia (PCR-uncorrected).
  • Number of Participants With Recurrent Parasitemia Versus Baseline Plasmodium Falciparum Chloroquine Resistance Transporter (PfCRT) Status [ Time Frame: Baseline to Day 42 ]
  • Percentage of Participants With PfCRT in True Failures [ Time Frame: Baseline to Day 42 ]
    A genetic marker, P.falciparum chloroquine resistance transporter (PfCRT), indicative of P.falciparum chloroquine resistance was to be determined from blood blots obtained on Day 0 and at the time of treatment failure. Treatment failure was defined as any of the following events that a participant experienced from Day 0 through the Day 42 visit: ETF (see measure description in secondary outcome measures 7 and 8), LCF (PCR corrected) (see measure description in secondary outcome measure 9 and 10), or LPF (PCR corrected) (see measure description in secondary outcome measure 11 and 12). Recrudescence of asexual P.falciparum parasites was considered treatment failure.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2008)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Azithromycin Plus Chloroquine Versus Artemether-Lumefantrine For The Treatment Of Uncomplicated P. Falciparum Malaria In Children In Africa
Official Title  ICMJE 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
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 Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malaria, Falciparum
Intervention  ICMJE
  • Drug: Azithromycin plus Chloroquine
    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)
  • Drug: Artemether-lumefantrine
    Artemether-lumefantrine tablet(s) based on weight and labeling for 3 days (Days 0, 1, 2)
Study Arms  ICMJE
  • Experimental: 1
    Intervention: Drug: Azithromycin plus Chloroquine
  • Experimental: 2
    Intervention: Drug: Artemether-lumefantrine
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 3, 2011)
361
Original Estimated Enrollment  ICMJE
 (submitted: May 12, 2008)
424
Actual Study Completion Date  ICMJE September 2010
Actual Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 12 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Burkina Faso,   Côte D'Ivoire,   Ghana,   Kenya,   Mali
Removed Location Countries Zambia
 
Administrative Information
NCT Number  ICMJE NCT00677833
Other Study ID Numbers  ICMJE A0661157
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP