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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00948896
Recruitment Status : Completed
First Posted : July 29, 2009
Results First Posted : August 4, 2015
Last Update Posted : November 24, 2015
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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Malaria
Interventions Drug: trimethoprim-sulfamethoxazole (TS; TMP/SMX)
Drug: sulfadoxine-pyrimethamine (SP)
Drug: dihydroartemisinin-piperaquine (DP)
Enrollment 600
Recruitment Details 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

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.

Arm/Group Title 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
Hide Arm/Group Description HIV-unexposed No chemoprevention was given HIV-unexposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs HIV-unexposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs HIV-unexposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs HIV-exposed No chemoprevention was given HIV-exposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs HIV-exposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs HIV-exposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
Period Title: Randomization to 24 Months of Age
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
Reason Not Completed
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 Title: 24 Months of Age to 36 Months of Age
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
Reason Not Completed
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
Arm/Group Title 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
Hide Arm/Group Description HIV-unexposed No chemoprevention was given HIV-unexposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs HIV-unexposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs HIV-unexposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs HIV-exposed No chemoprevention was given HIV-exposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs HIV-exposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs HIV-exposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs Total of all reporting groups
Overall Number of Baseline Participants 98 98 99 98 46 46 47 47 579
Hide Baseline Analysis Population Description
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.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 98 participants 98 participants 99 participants 98 participants 46 participants 46 participants 47 participants 47 participants 579 participants
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]
Measure Description: Age in months at time of enrollment
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 98 participants 98 participants 99 participants 98 participants 46 participants 46 participants 47 participants 47 participants 579 participants
Female
48
  49.0%
44
  44.9%
48
  48.5%
52
  53.1%
22
  47.8%
21
  45.7%
27
  57.4%
25
  53.2%
287
  49.6%
Male
50
  51.0%
54
  55.1%
51
  51.5%
46
  46.9%
24
  52.2%
25
  54.3%
20
  42.6%
22
  46.8%
292
  50.4%
Slept under any bednet prior night  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 98 participants 98 participants 99 participants 98 participants 46 participants 46 participants 47 participants 47 participants 579 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 98 participants 98 participants 99 participants 98 participants 46 participants 46 participants 47 participants 47 participants 579 participants
Yes 27 30 27 29 22 24 19 22 200
No 71 68 72 69 24 22 28 25 379
Stunted   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 98 participants 98 participants 99 participants 98 participants 46 participants 46 participants 47 participants 47 participants 579 participants
Yes 10 11 6 4 6 7 6 7 57
No 88 87 93 94 40 39 41 40 522
[1]
Measure Description: Length-for-age z-score <-2
Wasted   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 98 participants 98 participants 99 participants 98 participants 46 participants 46 participants 47 participants 47 participants 579 participants
Yes 4 7 7 5 0 4 1 4 32
No 94 91 92 93 46 42 46 43 547
[1]
Measure Description: Weight-for-age Z-score < -2
Hemoglobin  
Mean (Standard Deviation)
Unit of measure:  Gm/dl
Number Analyzed 98 participants 98 participants 99 participants 98 participants 46 participants 46 participants 47 participants 47 participants 579 participants
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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 98 participants 98 participants 99 participants 98 participants 46 participants 46 participants 47 participants 47 participants 579 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] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 98 participants 98 participants 99 participants 98 participants 46 participants 46 participants 47 participants 47 participants 579 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]
Measure Description: 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  
Median (Full Range)
Unit of measure:  Months
Number Analyzed 98 participants 98 participants 99 participants 98 participants 46 participants 46 participants 47 participants 47 participants 579 participants
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  
Median (Full Range)
Unit of measure:  Days
Number Analyzed 98 participants 98 participants 99 participants 98 participants 46 participants 46 participants 47 participants 47 participants 579 participants
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)
1.Primary Outcome
Title Incident Malaria Cases Per Person Year at Risk in HIV-unexposed Participants
Hide Description The incidence of malaria, defined as the number of incident episodes per time at risk, during the period the intervention was given (6–24 mo of age). Treatments within 14d of a prior episode were not considered incident events. Time at risk was from the day following the initiation of study drugs to the last day of observation, minus 14 d after each treatment for malaria.
Time Frame 6 to 24 months of age
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HIV-unexposed & no Chemoprevention HIV-unexposed & Monthly SP HIV-unexposed & Daily TS HIV-unexposed & Monthly DP
Hide Arm/Group Description:
HIV-unexposed No chemoprevention was given
HIV-unexposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs
HIV-unexposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs
HIV-unexposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
Overall Number of Participants Analyzed 98 98 99 98
Measure Type: Number
Unit of Measure: Episode per person year at risk
6-24 mo. of Age 6.95 6.73 5.21 3.02
6-11 mo. of Age 6.41 5.51 3.27 1.49
12-24 mo. of Age 7.24 7.41 6.32 3.88
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HIV-unexposed & no Chemoprevention, HIV-unexposed & Monthly SP
Comments The sample size was calculated to detect at least a 32% lower incidence of malaria in the DP arm compared to that in the TS arm. We assumed that the incidence of malaria would be 1.85 episodes per person-year with TS chemoprevention based on a prior cohort study in the same area, and thus we calculated that we would need to enroll 100 participants in each arm to detect our targeted protective efficacy with 80% power at 95% significance (two-sided), allowing for 10% loss to follow-up.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments [Not Specified]
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Protective Efficacy (%)
Estimated Value 7
Confidence Interval (2-Sided) 95%
-19 to 28
Estimation Comments The no chemoprevention arm is the reference group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HIV-unexposed & no Chemoprevention, HIV-unexposed & Daily TS
Comments The sample size was calculated to detect at least a 32% lower incidence of malaria in the DP arm compared to that in the TS arm. We assumed that the incidence of malaria would be 1.85 episodes per person-year with TS chemoprevention based on a prior cohort study in the same area, and thus we calculated that we would need to enroll 100 participants in each arm to detect our targeted protective efficacy with 80% power at 95% significance (two-sided), allowing for 10% loss to follow-up.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Protective Efficacy (%)
Estimated Value 28
Confidence Interval (2-Sided) 95%
7 to 44
Estimation Comments The no chemoprevention arm is the reference arm.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HIV-unexposed & no Chemoprevention, HIV-unexposed & Monthly DP
Comments The sample size was calculated to detect at least a 32% lower incidence of malaria in the DP arm compared to that in the TS arm. We assumed that the incidence of malaria would be 1.85 episodes per person-year with TS chemoprevention based on a prior cohort study in the same area, and thus we calculated that we would need to enroll 100 participants in each arm to detect our targeted protective efficacy with 80% power at 95% significance (two-sided), allowing for 10% loss to follow-up.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Protective Efficacy (%)
Estimated Value 58
Confidence Interval (2-Sided) 95%
45 to 67
Estimation Comments The no chemoprevention arm is the reference arm.
2.Primary Outcome
Title Incident Malaria Cases Per Person Year at Risk in HIV-exposed Participants
Hide Description The primary outcome was the incidence of malaria, defined as the number of incident episodes per time at risk, during the period the intervention was given. Treatments within 14 days of a prior episode were not considered incident events. Time at risk was from the day following the initiation of study drugs to the last day of observation, minus 14 days after each treatment for malaria.
Time Frame Randomization to 24 months of age
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HIV-exposed & no Chemoprevention HIV-exposed & Monthly SP HIV-exposed & Daily TS HIV-exposed & Monthly DP
Hide Arm/Group Description:
HIV-exposed No chemoprevention was given
HIV-exposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs
HIV-exposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs
HIV-exposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
Overall Number of Participants Analyzed 46 46 47 47
Measure Type: Number
Unit of Measure: Episodes per person year at risk
Randomization - 24 mo. of Age 6.28 4.50 2.86 1.83
Randomization -16 mo. of Age 5.42 3.72 1.70 0.90
17-24 mo. of Age 7.04 5.22 3.79 2.67
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HIV-exposed & no Chemoprevention, HIV-exposed & Monthly SP
Comments We assumed that the incidence of malaria would be 1.85 episodes per person year with TS based on a prior cohort study in the same area, and thus, that we would need to enroll 50 participants in each arm to detect a reduction in the incidence of malaria in either the monthly SP or DP arms (two-sided significance level 0.05) compared with the daily TS arm of 48% or greater with 80% power at 95% significance (two-sided), allowing for 10% loss to follow-up.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.065
Comments [Not Specified]
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Protective Efficacy (%)
Estimated Value 9
Confidence Interval (2-Sided) 95%
-35 to 38
Estimation Comments The no chemoprevention arm is the reference arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HIV-exposed & no Chemoprevention, HIV-exposed & Daily TS
Comments We assumed that the incidence of malaria would be 1.85 episodes per person year with TS based on a prior cohort study in the same area, and thus, that we would need to enroll 50 participants in each arm to detect a reduction in the incidence of malaria in either the monthly SP or DP arms (two-sided significance level 0.05) compared with the daily TS arm of 48% or greater with 80% power at 95% significance (two-sided), allowing for 10% loss to follow-up.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Adjusted for age at randomization and incidence of malaria prior to randomization.
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Protective Efficacy (%)
Estimated Value 49
Confidence Interval (2-Sided) 95%
23 to 66
Estimation Comments Adjusted for age at randomization and incidence of malaria prior to randomization. The no chemoprevention arm is the reference arm.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HIV-exposed & no Chemoprevention, HIV-exposed & Monthly DP
Comments We assumed that the incidence of malaria would be 1.85 episodes per person year with TS based on a prior cohort study in the same area, and thus, that we would need to enroll 50 participants in each arm to detect a reduction in the incidence of malaria in either the monthly SP or DP arms (two-sided significance level 0.05) compared with the daily TS arm of 48% or greater with 80% power at 95% significance (two-sided), allowing for 10% loss to follow-up.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Adjusted for age at randomization and incidence of malaria prior to randomization.
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Protective Efficacy (%)
Estimated Value 69
Confidence Interval (2-Sided) 95%
53 to 80
Estimation Comments Adjusted for age at randomization and incidence of malaria prior to randomization. The no chemoprevention arm is the reference arm.
3.Secondary Outcome
Title Incidence of Any Adverse Events Defined as Severity Grade 3-4 That Are Possibly, Probably, or Definitely Related to Study Drugs
Hide Description NIH Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events published December, 2004
Time Frame Time from randomization until 24 months of age
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 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
Hide Arm/Group Description:
HIV-unexposed No chemoprevention was given
HIV-unexposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs
HIV-unexposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs
HIV-unexposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
HIV-exposed No chemoprevention was given
HIV-exposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs
HIV-exposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs
HIV-exposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
Overall Number of Participants Analyzed 98 98 99 98 46 46 47 47
Measure Type: Number
Unit of Measure: incidence per person-year at risk
All grade 3-4 adverse events 1.159 1.415 0.914 0.611 1.214 1.478 0.659 0.678
Grade 3-4 AEs possibly related to study drugs NA [1]  0.056 0.054 0.021 NA [1]  0 0.062 0.097
All serious adverse events 0.178 0.364 0.196 0.091 0.411 0.453 0.330 0.194
Elevated Temperature 0.542 0.546 0.393 0.323 0.431 0.532 0.206 0.174
Anemia 0.384 0.602 0.318 0.168 0.705 0.631 0.206 0.291
Thrombocytopenia 0.123 0.119 0.061 0.035 0 0.118 0 0.058
Elevated aspartate aminotransferase 0.048 0.056 0.041 0.021 0.039 0.020 0.041 0.039
Elevated alanine aminotransferase 0.027 0.028 0.027 0.021 0 0 0 0
Neutropenia 0.021 0.042 0.014 0.007 0 0 0 0
Malnutrition 0 0 0 0 0.020 0.020 0.021 0.039
[1]
No study drugs taken.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection HIV-unexposed & no Chemoprevention, HIV-unexposed & Monthly DP
Comments Null Hypothesis: Within HIV-unexposed participants, there is no difference in the incidence of all grade 3-4 adverse events per PYAR between the control arm and the monthly DP arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Negative Binomial Regression
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection HIV-unexposed & no Chemoprevention, HIV-unexposed & Monthly DP
Comments Null Hypothesis: Within HIV-unexposed participants, there is no difference in the incidence of elevated temperature adverse events per PYAR between the control arm and the monthly DP arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments Monthly DP arm compared to No chemoprevention arm
Method Negative Binomial Regression
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection HIV-unexposed & no Chemoprevention, HIV-unexposed & Monthly DP
Comments Null Hypothesis: Within HIV-unexposed participants, there is no difference in the incidence of anemia adverse events per PYAR between the control arm and the monthly DP arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments Monthly DP arm compared to No chemoprevention arm
Method Negative Binomial Regression
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection HIV-unexposed & no Chemoprevention, HIV-unexposed & Monthly DP
Comments Null Hypothesis: Within HIV-unexposed participants, there is no difference in the incidence of thrombocytopenia adverse events per PYAR between the control arm and the monthly DP arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments Monthly DP arm compared to No chemoprevention arm
Method Negative Binomial Regression
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection HIV-exposed & no Chemoprevention, HIV-exposed & Monthly DP
Comments Null Hypothesis: Within HIV-exposed participants, there is no difference in the incidence of all grade 3-4 adverse events per PYAR between the control arm and the monthly DP arm.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments Monthly DP arm compared with no chemoprevention arm.
Method Negative Binomial Regression
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection HIV-exposed & no Chemoprevention, HIV-exposed & Monthly DP
Comments Null Hypothesis: Within HIV-exposed participants, there is no difference in the incidence of anemia adverse events per PYAR between the control arm and the monthly DP arm
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments Monthly DP arm compared with no chemoprevention arm.
Method Negative Binomial Regression
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection HIV-exposed & no Chemoprevention, HIV-exposed & Monthly DP
Comments Null Hypothesis: Within HIV-exposed participants, there is no difference in the incidence of elevated temperature adverse events per PYAR between the control arm and the monthly DP arm
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments Monthly DP arm compared with the no chemoprevention arm.
Method Negative Binomial Regression
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection HIV-exposed & no Chemoprevention, HIV-exposed & Daily TS
Comments Null Hypothesis: Within HIV-exposed participants, there is no difference in the incidence of anemia adverse events per PYAR between the control arm and the daily TS arm
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments Daily TS arm compare with the no chemoprevention arm.
Method Negative Binomial Regression
Comments [Not Specified]
4.Secondary Outcome
Title Rebound Incidence of Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk
Hide Description [Not Specified]
Time Frame 24 months to 36 months of age
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 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
Hide Arm/Group Description:
HIV-unexposed No chemoprevention was given
HIV-unexposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs
HIV-unexposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs
HIV-unexposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
HIV-exposed No chemoprevention was given
HIV-exposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs
HIV-exposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs
HIV-exposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
Overall Number of Participants Analyzed 87 83 85 85 43 40 43 45
Measure Type: Number
Unit of Measure: Incidence per person year at risk
All incident episodes of malaria 10.85 11.98 10.90 10.77 9.08 6.75 8.13 6.78
Complicated malaria 0.046 0.132 0.046 0 0.161 0.147 0.116 0.044
All-cause hospital admissions 0.046 0.452 0.091 0.023 0.459 0.318 0.186 0.089
Time Frame The adverse event data was collected in the time period between randomization and when intervention was stopped (24 mo. of Age).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 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
Hide Arm/Group Description HIV-unexposed No chemoprevention was given HIV-unexposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs HIV-unexposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs HIV-unexposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs HIV-exposed No chemoprevention was given HIV-exposed sulfadoxine-pyrimethamine (SP): monthly dosing given as a single dose, 500mg/25mg tabs HIV-exposed trimethoprim-sulfamethoxazole (TS; TMP/SMX): daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs HIV-exposed dihydroartemisinin-piperaquine (DP): monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
All-Cause Mortality
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
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
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/98 (22.45%)      25/98 (25.51%)      20/99 (20.20%)      10/98 (10.20%)      10/46 (21.74%)      14/46 (30.43%)      10/47 (21.28%)      8/47 (17.02%)    
Blood and lymphatic system disorders                 
Anemia *  15/98 (15.31%)  19 20/98 (20.41%)  45 14/99 (14.14%)  20 4/98 (4.08%)  5 8/46 (17.39%)  19 11/46 (23.91%)  17 4/47 (8.51%)  6 5/47 (10.64%)  6
Dehydration *  0/98 (0.00%)  0 0/98 (0.00%)  0 1/99 (1.01%)  1 2/98 (2.04%)  2 0/46 (0.00%)  0 1/46 (2.17%)  1 1/47 (2.13%)  1 0/47 (0.00%)  0
Neutropenia *  3/98 (3.06%)  3 0/98 (0.00%)  0 0/99 (0.00%)  0 0/98 (0.00%)  0 0/46 (0.00%)  0 0/46 (0.00%)  0 1/47 (2.13%)  1 0/47 (0.00%)  0
Thrombocytopenia *  3/98 (3.06%)  3 3/98 (3.06%)  5 1/99 (1.01%)  1 0/98 (0.00%)  0 0/46 (0.00%)  0 0/46 (0.00%)  0 0/47 (0.00%)  0 0/47 (0.00%)  0
Endocrine disorders                 
Elevated temperature *  2/98 (2.04%)  2 3/98 (3.06%)  3 0/99 (0.00%)  0 0/98 (0.00%)  0 0/46 (0.00%)  0 1/46 (2.17%)  1 0/47 (0.00%)  0 1/47 (2.13%)  1
Gastrointestinal disorders                 
Vomiting *  0/98 (0.00%)  0 0/98 (0.00%)  0 0/99 (0.00%)  0 0/98 (0.00%)  0 0/46 (0.00%)  0 2/46 (4.35%)  2 0/47 (0.00%)  0 0/47 (0.00%)  0
Intestinal obstruction *  0/98 (0.00%)  0/98 (0.00%)  0 0/99 (0.00%)  0 0/98 (0.00%)  0 0/46 (0.00%)  0 0/46 (0.00%)  0 1/47 (2.13%)  1 0/47 (0.00%)  0
Hepatobiliary disorders                 
Elevated ALT (SGPT) *  5/98 (5.10%)  5 1/98 (1.02%)  1 1/99 (1.01%)  1 2/98 (2.04%)  2 0/46 (0.00%)  0 0/46 (0.00%)  0 1/47 (2.13%)  1 0/47 (0.00%)  0
Elevated AST (SGOT) *  6/98 (6.12%)  7 0/98 (0.00%)  0 4/99 (4.04%)  4 3/98 (3.06%)  3 0/46 (0.00%)  0 0/46 (0.00%)  0 1/47 (2.13%)  1 0/47 (0.00%)  0
Infections and infestations                 
Septicemia *  0/98 (0.00%)  0 0/98 (0.00%)  0 0/99 (0.00%)  0 0/98 (0.00%)  0 0/46 (0.00%)  0 1/46 (2.17%)  1 1/47 (2.13%)  1 0/47 (0.00%)  0
Injury, poisoning and procedural complications                 
Fracture *  0/98 (0.00%)  0 0/98 (0.00%)  0 1/99 (1.01%)  1 0/98 (0.00%)  0 0/46 (0.00%)  0 0/46 (0.00%)  0 0/47 (0.00%)  0 0/47 (0.00%)  0
Metabolism and nutrition disorders                 
Malnutrition *  1/98 (1.02%)  1 0/98 (0.00%)  0 2/99 (2.02%)  2 1/98 (1.02%)  1 1/46 (2.17%)  1 1/46 (2.17%)  1 1/47 (2.13%)  1 2/47 (4.26%)  2
Poor feeding *  0/98 (0.00%)  0/98 (0.00%)  0 0/99 (0.00%)  0 0/98 (0.00%)  0 0/46 (0.00%)  0 0/46 (0.00%)  0 1/46 (2.17%)  1 0/47 (0.00%)  0
Nervous system disorders                 
Electrolyte imbalance *  0/98 (0.00%)  0 0/98 (0.00%)  0 0/99 (0.00%)  0 0/98 (0.00%)  0 1/46 (2.17%)  1 0/46 (0.00%)  0 1/47 (2.13%)  1 1/47 (2.13%)  1
Respiratory, thoracic and mediastinal disorders                 
Dyspnea *  0/98 (0.00%)  0 1/98 (1.02%)  1 0/99 (0.00%)  0 0/98 (0.00%)  0 0/46 (0.00%)  0 0/46 (0.00%)  0 1/47 (2.13%)  1 1/47 (2.13%)  1
Respiratory failure *  1/98 (1.02%)  1 0/98 (0.00%)  0 0/99 (0.00%)  0 0/98 (0.00%)  0 0/46 (0.00%)  0 0/46 (0.00%)  0 0/47 (0.00%)  0 0/47 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
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
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   70/98 (71.43%)      66/98 (67.35%)      58/99 (58.59%)      49/98 (50.00%)      28/46 (60.87%)      28/46 (60.87%)      11/47 (23.40%)      14/47 (29.79%)    
Blood and lymphatic system disorders                 
Anemia *  31/98 (31.63%)  39 28/98 (28.57%)  44 21/99 (21.21%)  28 17/98 (17.35%)  19 14/46 (30.43%)  18 11/46 (23.91%)  15 3/47 (6.38%)  4 7/47 (14.89%)  10
Neutropenia *  3/98 (3.06%)  3 6/98 (6.12%)  6 2/99 (2.02%)  2 1/98 (1.02%)  1 0/46 (0.00%)  0 0/46 (0.00%)  0 0/47 (0.00%)  0 1/47 (2.13%)  1
Thrombocytopenia *  15/98 (15.31%)  15 7/98 (7.14%)  12 5/99 (5.05%)  8 5/98 (5.10%)  5 0/46 (0.00%)  0 5/46 (10.87%)  6 0/47 (0.00%)  0 3/47 (6.38%)  3
Endocrine disorders                 
Chills *  0/98 (0.00%)  0 1/98 (1.02%)  1 0/99 (0.00%)  0 0/98 (0.00%)  0 0/46 (0.00%)  0 0/46 (0.00%)  0 0/47 (0.00%)  0 0/47 (0.00%)  0
Elevated temperature *  53/98 (54.08%)  77 49/98 (50.00%)  75 41/99 (41.41%)  58 32/98 (32.65%)  46 17/46 (36.96%)  22 19/46 (41.30%)  27 9/47 (19.15%)  10 6/47 (12.77%)  8
Gastrointestinal disorders                 
Diarrhea *  0/98 (0.00%)  0 0/98 (0.00%)  0 0/99 (0.00%)  0 0/98 (0.00%)  0 0/46 (0.00%)  0 1/46 (2.17%)  1 0/47 (0.00%)  0 1/47 (2.13%)  1
Hepatobiliary disorders                 
Elevated ALT (SGPT) *  4/98 (4.08%)  4 3/98 (3.06%)  3 3/99 (3.03%)  3 1/98 (1.02%)  1 0/46 (0.00%)  0 2/46 (4.35%)  2 1/47 (2.13%)  1 0/47 (0.00%)  0
Elevated AST (SGOT) *  5/98 (5.10%)  6 7/98 (7.14%)  8 2/99 (2.02%)  2 0/98 (0.00%)  0 2/46 (4.35%)  2 1/46 (2.17%)  1 1/47 (2.13%)  1 1/47 (2.13%)  2
Infections and infestations                 
Septicemia *  0/98 (0.00%)  0 1/98 (1.02%)  1 0/99 (0.00%)  0 1/98 (1.02%)  1 0/46 (0.00%)  0 0/46 (0.00%)  0 0/47 (0.00%)  0 0/47 (0.00%)  0
Nervous system disorders                 
Electrolyte imbalance *  0/98 (0.00%)  0 0/98 (0.00%)  0 1/99 (1.01%)  1 0/98 (0.00%)  0 0/46 (0.00%)  0 0/46 (0.00%)  0 0/47 (0.00%)  0 0/47 (0.00%)  0
Seizure *  0/98 (0.00%)  0 0/98 (0.00%)  0 1/99 (1.01%)  1 0/98 (0.00%)  0 0/46 (0.00%)  0 0/46 (0.00%)  0 0/47 (0.00%)  0 0/47 (0.00%)  0
Renal and urinary disorders                 
Hyperglycemia *  0/98 (0.00%)  0 0/98 (0.00%)  0 2/99 (2.02%)  2 0/98 (0.00%)  0 0/46 (0.00%)  0 1/46 (2.17%)  1 0/47 (0.00%)  0 0/47 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                 
Dyspnea *  0/98 (0.00%)  0 0/98 (0.00%)  0 0/99 (0.00%)  0 1/98 (1.02%)  1 0/46 (0.00%)  0 0/46 (0.00%)  0 0/47 (0.00%)  0 0/47 (0.00%)  0
Skin and subcutaneous tissue disorders                 
Rash *  0/98 (0.00%)  0 0/98 (0.00%)  0 1/99 (1.01%)  1 0/98 (0.00%)  0 0/46 (0.00%)  0 0/46 (0.00%)  0 0/47 (0.00%)  0 0/47 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
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
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 )
First Submitted: July 27, 2009
First Posted: July 29, 2009
Results First Submitted: April 30, 2015
Results First Posted: August 4, 2015
Last Update Posted: November 24, 2015