Chloroquine Alone or in Combination for Malaria in Children in Malawi

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00379821
First received: September 21, 2006
Last updated: January 16, 2014
Last verified: August 2012
Results First Received: June 30, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Plasmodium Falciparum Malaria
Interventions: Drug: Chloroquine
Drug: Azithromycin
Drug: Atovaquone-proguanil
Drug: Artesunate

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Children who were brought to the Ndirande Health Centre with symptoms suggestive of malaria were recruited from February 19, 2007 to August 13, 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Chloroquine Plus Artesunate Participants receive chloroquine (CQ) at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2; plus Artesunate at a dose of 4 mg/kg once a day for 3 days.
Chloroquine Plus Atovaquone-Proguanil Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2; plus Atovaquone-Proguanil (AP) once a day for 3 days dosed as follows: 5-8 kg, 2 pediatric tablet (PT, 62.5 mg/25mg); 9-10 kg, 3 PT; 11-20 kg, 1 full strength tablet (FST, 250mg/100 mg); 21-30 kg 2 FST; >30 kg, 3 FST.
CQ Plus Azithromycin Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2; plus Azithromycin 30 mg/kg once a day for 3 days.
CQ Monotherapy Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2.

Participant Flow:   Overall Study
    Chloroquine Plus Artesunate     Chloroquine Plus Atovaquone-Proguanil     CQ Plus Azithromycin     CQ Monotherapy  
STARTED     160     160     160     160  
COMPLETED     87     71     93     81  
NOT COMPLETED     73     89     67     79  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Chloroquine Plus Artesunate Participants receive chloroquine (CQ) at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2; plus Artesunate at a dose of 4 mg/kg once a day for 3 days.
Chloroquine Plus Atovaquone-Proguanil Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2; plus Atovaquone-Proguanil (AP) once a day for 3 days dosed as follows: 5-8 kg, 2 pediatric tablet (PT, 62.5 mg/25mg); 9-10 kg, 3 PT; 11-20 kg, 1 full strength tablet (FST, 250mg/100 mg); 21-30 kg 2 FST; >30 kg, 3 FST.
CQ Plus Azithromycin Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2; plus Azithromycin 30 mg/kg once a day for 3 days.
CQ Monotherapy Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2.
Total Total of all reporting groups

Baseline Measures
    Chloroquine Plus Artesunate     Chloroquine Plus Atovaquone-Proguanil     CQ Plus Azithromycin     CQ Monotherapy     Total  
Number of Participants  
[units: participants]
  160     160     160     160     640  
Age  
[units: participants]
         
<=18 years     160     160     160     160     640  
Between 18 and 65 years     0     0     0     0     0  
>=65 years     0     0     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  2.7  ± 1.2     2.7  ± 1.2     2.8  ± 1.1     2.7  ± 1.2     2.7  ± 1.2  
Gender  
[units: participants]
         
Female     70     82     73     77     302  
Male     90     78     87     83     338  
Region of Enrollment  
[units: participants]
         
Malawi     160     160     160     160     640  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Clinical Malaria Episodes Per Year of Follow-up   [ Time Frame: 1 year ]

2.  Secondary:   Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm   [ Time Frame: Day 28 of initial malaria episode (Episode 0) ]

3.  Secondary:   Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm   [ Time Frame: Day 28 of first subsequent malaria episode (Episode 1) ]

4.  Secondary:   Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm   [ Time Frame: Day 28 of second subsequent malaria episode (Episode 2) ]

5.  Secondary:   Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm   [ Time Frame: Day 28 of third subsequent malaria episode (Episode 3) ]

6.  Secondary:   Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm   [ Time Frame: Day 28 of fourth subsequent malaria episode (Episode 4) ]

7.  Secondary:   Number of Cases of Severe Malaria in Each Treatment Arm   [ Time Frame: 1 Year ]

8.  Secondary:   Mean Hemoglobin at the Last Study Visit in Each Treatment Arm for the Age Group of Participants 3 Years of Age or Younger.   [ Time Frame: 1 year ]

9.  Secondary:   Mean Hemoglobin at the Last Study Visit in Each Treatment Arm for the Age Group of Participants Greater Than 3 Years to 5 Years of Age.   [ Time Frame: 1 year ]

10.  Secondary:   Mean Creatinine in Each Treatment Arm (Renal Function)   [ Time Frame: Day 0 of initial malaria episode (Episode 0) ]

11.  Secondary:   Mean Creatinine in Each Treatment Arm (Renal Function)   [ Time Frame: Day 14 of initial malaria episode (Episode 0) ]

12.  Secondary:   Mean Creatinine in Each Treatment Arm (Renal Function)   [ Time Frame: Day 0 of first subsequent malaria episode (Episode 1) ]

13.  Secondary:   Mean Creatinine in Each Treatment Arm (Renal Function)   [ Time Frame: Day 14 of first subsequent malaria episode (Episode 1) ]

14.  Secondary:   Mean Creatinine in Each Treatment Arm (Renal Function)   [ Time Frame: Day 0 of second subsequent malaria episode (Episode 2) ]

15.  Secondary:   Mean Creatinine in Each Treatment Arm (Renal Function)   [ Time Frame: Day 14 of second subsequent malaria episode (Episode 2) ]

16.  Secondary:   Mean Creatinine in Each Treatment Arm (Renal Function)   [ Time Frame: Day 0 of third subsequent malaria episode (Episode 3) ]

17.  Secondary:   Mean Creatinine in Each Treatment Arm (Renal Function)   [ Time Frame: Day 14 of third subsequent malaria episode (Episode 3) ]

18.  Secondary:   Mean Creatinine in Each Treatment Arm (Renal Function)   [ Time Frame: Day 0 of fourth subsequent malaria episode (Episode 4) ]

19.  Secondary:   Mean Creatinine in Each Treatment Arm (Renal Function)   [ Time Frame: Day 14 of fourth subsequent malaria episode (Episode 4) ]

20.  Secondary:   Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function)   [ Time Frame: Day 0 of initial malaria episode (Episode 0) ]

21.  Secondary:   Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function)   [ Time Frame: Day 14 of initial malaria episode (Episode 0) ]

22.  Secondary:   Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function)   [ Time Frame: Day 0 of first subsequent malaria episode (Episode 1) ]

23.  Secondary:   Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function)   [ Time Frame: Day 14 of first subsequent malaria episode (Episode 1) ]

24.  Secondary:   Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function)   [ Time Frame: Day 0 of second subsequent malaria episode (Episode 2) ]

25.  Secondary:   Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function)   [ Time Frame: Day 14 of second subsequent malaria episode (Episode 2) ]

26.  Secondary:   Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function)   [ Time Frame: Day 0 of third subsequent malaria episode (Episode 3) ]

27.  Secondary:   Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function)   [ Time Frame: Day 14 of third subsequent malaria episode (Episode 3) ]

28.  Secondary:   Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function)   [ Time Frame: Day 0 of fourth subsequent malaria episode (Episode 4) ]

29.  Secondary:   Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function)   [ Time Frame: Day 14 of fourth subsequent malaria episode (Episode 4) ]

30.  Secondary:   Number of Participants in Each Treatment Arm Who Change From “Normal” to “Abnormal” on Any Questions of the Neurological Examination   [ Time Frame: 1 Year ]

31.  Secondary:   Number of Participants Infected With Parasites With the Mutation Pfcrt 76T on Day 0 of the Initial Episode of Malaria   [ Time Frame: Day 0 of initial episode of malaria ]

32.  Secondary:   Number of Participants Infected With Parasites With the Mutation Pfcrt 76T at Recrudescent Episodes of Malaria   [ Time Frame: Recrudescent episodes of malaria within one year of enrollment ]

33.  Secondary:   Number of Participants With New and Recrudescent Malaria Infections After Initial Treatment   [ Time Frame: 28 days to 1 year ]

34.  Secondary:   Number of Participants With New and Recrudescent Infections After Subsequent New Episodes   [ Time Frame: Day 28 to 1 year ]

35.  Secondary:   Time to First Malaria Episode in Participants Who Travelled and Slept Outside the City Versus Those Who Did Not Travel and Sleep Outside the City.   [ Time Frame: Days 0 - 420 ]

36.  Secondary:   Nearest Neighbor Index as a Measure of Spatial Pattern of the Distribution of Malaria Cases in Ndirande   [ Time Frame: 1 year ]

37.  Secondary:   Pharmacokinetics of Chloroquine Represented by Time of Maximal Concentration (Tmax) and Chloroquine Half-life   [ Time Frame: Day 0 - Day 28 ]

38.  Secondary:   Pharmacokinetics of Chloroquine Represented by Maximum Concentration (Cmax)   [ Time Frame: Day 0 - Day 28 ]


  Serious Adverse Events


  Other Adverse Events


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Christopher Plowe, MD, MPH
Organization: Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine
phone: 410-706-2491
e-mail: cplowe@medicine.umaryland.edu


Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00379821     History of Changes
Other Study ID Numbers: 06-0022
Study First Received: September 21, 2006
Results First Received: June 30, 2011
Last Updated: January 16, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
Malawi: Ministry of Health
United States: Federal Government