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Chemopreventive Therapy for Malaria in Ugandan Children (PROMOTE-Chemop)

This study has been completed.
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Grant Dorsey, M.D, Ph.D., University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00948896
First received: July 27, 2009
Last updated: October 26, 2015
Last verified: October 2015
Results First Received: April 30, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Condition: Malaria
Interventions: Drug: trimethoprim-sulfamethoxazole (TS; TMP/SMX)
Drug: sulfadoxine-pyrimethamine (SP)
Drug: dihydroartemisinin-piperaquine (DP)

  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
Convenience sampling was used to enroll a cohort of 600 infants 4–5 months of age from the Tororo District Hospital Maternal and Child Health clinic between June 2010 and July 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Of the 400 HIV-unexposed infants, 7 were excluded prior to randomization for inability to comply with study protocol.

Of the 200 HIV-exposed infants, 14 were excluded prior to randomization for the following reasons: 7 tested HIV positive; 3 unable to locate for > 60 days; 2 withdrew informed consent; 1 died; 1 unable to comply with protocol.


Reporting Groups
  Description
HIV-unexposed & No Chemoprevention HIV-unexposed No chemoprevention was given
HIV-unexposed & SP HIV-unexposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs
HIV-unexposed & TS HIV-unexposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs
HIV-unexposed & DP HIV-unexposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
HIV-exposed & no Chemoprevention HIV-exposed No chemoprevention was given
HIV-exposed & SP HIV-exposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs
HIV-exposed & TS HIV-exposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs
HIV-exposed & DP HIV-exposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs

Participant Flow for 2 periods

Period 1:   Randomization to 24 Months of Age
    HIV-unexposed & No Chemoprevention   HIV-unexposed & SP   HIV-unexposed & TS   HIV-unexposed & DP   HIV-exposed & no Chemoprevention   HIV-exposed & SP   HIV-exposed & TS   HIV-exposed & DP
STARTED   98   98   99   98   46   46   47   47 
COMPLETED   90   85   90   87   44   42   43   45 
NOT COMPLETED   8   13   9   11   2   4   4   2 
Death                1                0                0                0                2                1                2                1 
Withdrawal by Subject                3                5                4                4                0                1                0                0 
Lost to Follow-up                4                4                2                5                0                0                1                0 
Protocol Violation                0                1                0                1                0                0                1                1 
Moved out of Study Area                0                3                3                1                0                2                0                0 

Period 2:   24 Months of Age to 36 Months of Age
    HIV-unexposed & No Chemoprevention   HIV-unexposed & SP   HIV-unexposed & TS   HIV-unexposed & DP   HIV-exposed & no Chemoprevention   HIV-exposed & SP   HIV-exposed & TS   HIV-exposed & DP
STARTED   90   85   90   87   44   42   43   45 
COMPLETED   87   83   85   85   43   40   43   45 
NOT COMPLETED   3   2   5   2   1   2   0   0 
Death                0                2                2                0                0                1                0                0 
Withdrawal by Subject                1                0                1                1                0                0                0                0 
Lost to Follow-up                2                0                1                0                1                0                0                0 
Protocol Violation                0                0                1                0                0                1                0                0 
Moved out of Study Area                0                0                0                1                0                0                0                0 



  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.
Convenience sampling was used to enroll a cohort of 600 infants 4–5 mo of age from the Tororo District Hospital Maternal and Child Health Clinic between June 2010 and July 2011. The baseline characteristics were taken at enrollment.

Reporting Groups
  Description
HIV-unexposed & no Chemoprevention HIV-unexposed No chemoprevention was given
HIV-unexposed & Monthly SP HIV-unexposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs
HIV-unexposed & Daily TS HIV-unexposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs
HIV-unexposed & Monthly DP HIV-unexposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
HIV-exposed & no Chemoprevention HIV-exposed No chemoprevention was given
HIV-exposed & Monthly SP HIV-exposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs
HIV-exposed & Daily TS HIV-exposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs
HIV-exposed & Monthly DP HIV-exposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
Total Total of all reporting groups

Baseline Measures
   HIV-unexposed & no Chemoprevention   HIV-unexposed & Monthly SP   HIV-unexposed & Daily TS   HIV-unexposed & Monthly DP   HIV-exposed & no Chemoprevention   HIV-exposed & Monthly SP   HIV-exposed & Daily TS   HIV-exposed & Monthly DP   Total 
Overall Participants Analyzed 
[Units: Participants]
 98   98   99   98   46   46   47   47   579 
Age [1] 
[Units: Months]
Mean (Standard Deviation)
 5.4  (0.5)   5.3  (0.5)   5.4  (0.5)   5.4  (0.5)   4.8  (0.7)   4.7  (0.7)   4.8  (0.8)   4.7  (0.8)   5.2  (0.6) 
[1] Age in months at time of enrollment
Gender 
[Units: Participants]
                 
Female   48   44   48   52   22   21   27   25   287 
Male   50   54   51   46   24   25   20   22   292 
Slept under any bednet prior night 
[Units: Participants]
                 
Yes   41   43   40   45   27   27   26   29   278 
No   57   55   59   53   19   19   21   18   301 
Slept under ITN prior night 
[Units: Participants]
                 
Yes   27   30   27   29   22   24   19   22   200 
No   71   68   72   69   24   22   28   25   379 
Stunted [1] 
[Units: Participants]
                 
Yes   10   11   6   4   6   7   6   7   57 
No   88   87   93   94   40   39   41   40   522 
[1] Length-for-age z-score <-2
Wasted [1] 
[Units: Participants]
                 
Yes   4   7   7   5   0   4   1   4   32 
No   94   91   92   93   46   42   46   43   547 
[1] Weight-for-age Z-score < -2
Hemoglobin 
[Units: Gm/dl]
Mean (Standard Deviation)
 9.7  (1.4)   9.6  (1.8)   9.9  (1.5)   9.5  (1.5)   10.1  (1.2)   10.0  (1.4)   10.1  (1.1)   10.5  (1.5)   9.8  (1.5) 
Positive thick blood smear 
[Units: Participants]
                 
Yes   22   27   17   28   8   4   8   6   120 
No   76   71   82   70   38   42   39   41   459 
Taking TS prophylaxis [1] [2] [3] 
[Units: Participants]
                 
Yes   NA [2]   NA [2]   NA [2]   NA [2]   5   7   5   9   NA [3] 
No   NA [2]   NA [2]   NA [2]   NA [2]   41   39   42   38   NA [3] 
[1] This measurement is only applicable for the HIV-exposed participants (n=186).
[2] Only applicable for HIV-exposed participants
[3] Total not calculated because data are not available (NA) in one or more arms.
Age at time of randomization 
[Units: Months]
Median (Full Range)
 6.0 
 (6.0 to 6.5) 
 6.0 
 (6.0 to 6.5) 
 6.0 
 (6.0 to 6.3) 
 6.0 
 (6.0 to 6.5) 
 10.0 
 (6.0 to 18.0) 
 9.3 
 (6.5 to 18.8) 
 11.6 
 (6.2 to 18.7) 
 10.3 
 (6.5 to 20.0) 
 6.0 
 (6.0 to 20.0) 
Duration of follow-up 
[Units: Days]
Median (Full Range)
 547 
 (53 to 580) 
 547 
 (63 to 550) 
 547 
 (58 to 564) 
 547 
 (7 to 569) 
 427 
 (88 to 549) 
 420 
 (127 to 524) 
 346 
 (88 to 505) 
 409 
 (31 to 535) 
 546 
 (7 to 580) 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Incident Malaria Cases Per Person Year at Risk in HIV-unexposed Participants   [ Time Frame: 6 to 24 months of age ]

2.  Primary:   Incident Malaria Cases Per Person Year at Risk in HIV-exposed Participants   [ Time Frame: Randomization to 24 months of age ]

3.  Secondary:   Incidence of Any Adverse Events Defined as Severity Grade 3-4 That Are Possibly, Probably, or Definitely Related to Study Drugs   [ Time Frame: Time from randomization until 24 months of age ]

4.  Secondary:   Rebound Incidence of Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk   [ Time Frame: 24 months to 36 months of age ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Dr. Grant Dorsey
Organization: University of California, San Francisco
phone: 415-206-4680
e-mail: grant.dorsey@ucsf.edu


Publications of Results:


Responsible Party: Grant Dorsey, M.D, Ph.D., University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00948896     History of Changes
Other Study ID Numbers: H9926-33953
NIH P01HD059454
2009-077 ( Other Identifier: Makerere Univ Fac of Med Research and Ethics Committee )
HS-580 ( Other Identifier: Uganda National Council for Science and Tech )
686/ESR/NDA/DID-11/2009 ( Other Identifier: Uganda National Drug Authority )
H9926-33953 and 10-01489 ( Other Identifier: UCSF Committee on Human Research )
Study First Received: July 27, 2009
Results First Received: April 30, 2015
Last Updated: October 26, 2015
Health Authority: United States: Food and Drug Administration