Trial Outcomes & Findings for Assessing a Risk Model for G6PD Deficiency (NCT NCT03337152)
NCT ID: NCT03337152
Last Updated: 2021-11-12
Results Overview
The change in haemoglobin from baseline on exposure to primaquine for P.vivax treatment over treatment course to hemoglobin level at day 28.
TERMINATED
PHASE4
54 participants
28 days after enrollment
2021-11-12
Participant Flow
6 participants were enrolled into the trial but had not been randomized at the time of the study halt. Those 6 participants were thus never assigned to a study group.
Participant milestones
| Measure |
1A: Primaquine
primaquine: Participants receive primaquine for 14 days at 0.5 mg/Kg.
|
1B: Chloroquine + Primaquine
chloroquine + primaquine: Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg.
|
|---|---|---|
|
Overall Study
STARTED
|
24
|
24
|
|
Overall Study
COMPLETED
|
13
|
13
|
|
Overall Study
NOT COMPLETED
|
11
|
11
|
Reasons for withdrawal
| Measure |
1A: Primaquine
primaquine: Participants receive primaquine for 14 days at 0.5 mg/Kg.
|
1B: Chloroquine + Primaquine
chloroquine + primaquine: Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg.
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
3
|
|
Overall Study
Adverse Event
|
3
|
1
|
|
Overall Study
Stopped drug dosing due to study halt
|
6
|
7
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
1A: Primaquine
n=24 Participants
primaquine: Participants receive primaquine for 14 days at 0.5 mg/Kg.
|
1B: Chloroquine + Primaquine
n=24 Participants
chloroquine + primaquine: Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg.
|
Total
n=48 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Region of Enrollment
Thailand
|
24 participants
n=24 Participants
|
24 participants
n=24 Participants
|
48 participants
n=48 Participants
|
|
G6PD Status
Heterozygous Female
|
5 Participants
n=24 Participants
|
4 Participants
n=24 Participants
|
9 Participants
n=48 Participants
|
|
Age, Continuous
|
33.5 years
n=24 Participants
|
38.5 years
n=24 Participants
|
36 years
n=48 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=24 Participants
|
16 Participants
n=24 Participants
|
32 Participants
n=48 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=24 Participants
|
8 Participants
n=24 Participants
|
16 Participants
n=48 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
G6PD Status
Homozygous Female
|
11 Participants
n=24 Participants
|
12 Participants
n=24 Participants
|
23 Participants
n=48 Participants
|
|
G6PD Status
Hemizygous Male
|
8 Participants
n=24 Participants
|
8 Participants
n=24 Participants
|
16 Participants
n=48 Participants
|
|
Hemoglobin
|
13.2 g/dL
n=24 Participants
|
12.65 g/dL
n=24 Participants
|
12.9 g/dL
n=48 Participants
|
|
G6PD Concentration
|
7.66 IU/g Hb
n=24 Participants
|
7.515 IU/g Hb
n=24 Participants
|
7.58 IU/g Hb
n=48 Participants
|
PRIMARY outcome
Timeframe: 28 days after enrollmentPopulation: Among those with available data at baseline and at least one timepoint after study treatment began.
The change in haemoglobin from baseline on exposure to primaquine for P.vivax treatment over treatment course to hemoglobin level at day 28.
Outcome measures
| Measure |
1A: Primaquine
n=24 Participants
primaquine: Participants receive primaquine for 14 days at 0.5 mg/Kg.
|
1B: Chloroquine + Primaquine
n=24 Participants
chloroquine + primaquine: Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg.
|
|---|---|---|
|
Change in Haemoglobin
|
-1.1 g/dL
Interval -4.1 to 0.0
|
-1.05 g/dL
Interval -4.5 to 0.0
|
PRIMARY outcome
Timeframe: 28 days after enrollmentPopulation: Among those with available data at baseline and at least one timepoint after study treatment began.
The haemoglobin-related change in G6PD concentration, as determined by spectrometer, over treatment course. Change is determined from baseline to day 28
Outcome measures
| Measure |
1A: Primaquine
n=24 Participants
primaquine: Participants receive primaquine for 14 days at 0.5 mg/Kg.
|
1B: Chloroquine + Primaquine
n=24 Participants
chloroquine + primaquine: Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg.
|
|---|---|---|
|
Change in G6PD Concentration
|
-1.23 IU/g Hb
Interval -2.99 to -0.34
|
-1.94 IU/g Hb
Interval -6.09 to -0.39
|
SECONDARY outcome
Timeframe: 28 days after enrollmentPopulation: Analysis not possible due to the study termination as the planned risk model could not be developed without sufficient data. Relevance of CYP2D6 results in the model thus unable to be determined.
relevance of Dextromethorphan assay results to risk of haemolysis models
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 1,2,3,5,7,9,11,14,17,21Population: This association was dependent on developing a model which requires completion of the study for an appropriate sample size. The incompletion of the study resulted in it not being possible to generate this model and therefore assess the association of drug levels with hematological and G6PD activity levels
Association of chloroquine and primaquine drug levels at the time of sampling for haematological and G6PD profiles.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 28 days after enrollmentPopulation: All randomized women heterozygous for G6PD.
frequency of serious adverse events in women heterozygous for G6PD
Outcome measures
| Measure |
1A: Primaquine
n=5 Participants
primaquine: Participants receive primaquine for 14 days at 0.5 mg/Kg.
|
1B: Chloroquine + Primaquine
n=4 Participants
chloroquine + primaquine: Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg.
|
|---|---|---|
|
Serious Adverse Events
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Days 1,2,3,5,7,9,11,14,17,21Population: The relevance of reticulocyte count was dependent on developing a model which requires completion of the study for an appropriate sample size. The incompletion of the study resulted in it not being possible to generate this model and therefore assess the relevance of reticulocyte count on risk of hemolysis
relevance of reticulocyte count to risk of haemolysis models
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 1,2,3,5,7,9,11,14,17,21Population: The relevance of urobilinogen tests of was dependent on developing a model which requires completion of the study for an appropriate sample size. The incompletion of the study resulted in it not being possible to generate this model and therefore assess the relevance of urobilinogen tests on hemolytic risk models
relevance of urobilinogen tests to risk of haemolysis models
Outcome measures
Outcome data not reported
Adverse Events
1A: Primaquine
1B: Chloroquine + Primaquine
Serious adverse events
| Measure |
1A: Primaquine
n=24 participants at risk
primaquine: Participants receive primaquine for 14 days at 0.5 mg/Kg.
|
1B: Chloroquine + Primaquine
n=24 participants at risk
chloroquine + primaquine: Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg.
|
|---|---|---|
|
Blood and lymphatic system disorders
Hemolysis
|
12.5%
3/24 • Number of events 3 • 28 days after enrollment
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
Other adverse events
| Measure |
1A: Primaquine
n=24 participants at risk
primaquine: Participants receive primaquine for 14 days at 0.5 mg/Kg.
|
1B: Chloroquine + Primaquine
n=24 participants at risk
chloroquine + primaquine: Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
12.5%
3/24 • Number of events 3 • 28 days after enrollment
|
0.00%
0/24 • 28 days after enrollment
|
|
Eye disorders
Blurred vision
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
25.0%
6/24 • Number of events 6 • 28 days after enrollment
|
|
Injury, poisoning and procedural complications
Wound
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
|
Respiratory, thoracic and mediastinal disorders
Common cold
|
8.3%
2/24 • Number of events 3 • 28 days after enrollment
|
8.3%
2/24 • Number of events 2 • 28 days after enrollment
|
|
Gastrointestinal disorders
Decreased appetite
|
8.3%
2/24 • Number of events 2 • 28 days after enrollment
|
20.8%
5/24 • Number of events 6 • 28 days after enrollment
|
|
General disorders
Difficulty sleeping
|
8.3%
2/24 • Number of events 2 • 28 days after enrollment
|
20.8%
5/24 • Number of events 5 • 28 days after enrollment
|
|
General disorders
Dizziness
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
45.8%
11/24 • Number of events 12 • 28 days after enrollment
|
|
General disorders
Fatigue
|
8.3%
2/24 • Number of events 2 • 28 days after enrollment
|
16.7%
4/24 • Number of events 4 • 28 days after enrollment
|
|
Gastrointestinal disorders
Gastritis
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
0.00%
0/24 • 28 days after enrollment
|
|
Renal and urinary disorders
Glucosuria
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
0.00%
0/24 • 28 days after enrollment
|
|
General disorders
Headache
|
16.7%
4/24 • Number of events 4 • 28 days after enrollment
|
12.5%
3/24 • Number of events 3 • 28 days after enrollment
|
|
Blood and lymphatic system disorders
Methemoglobinemia
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
0.00%
0/24 • 28 days after enrollment
|
|
Respiratory, thoracic and mediastinal disorders
Viral infection
|
4.2%
1/24 • Number of events 2 • 28 days after enrollment
|
0.00%
0/24 • 28 days after enrollment
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/24 • 28 days after enrollment
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
|
Psychiatric disorders
Depression
|
0.00%
0/24 • 28 days after enrollment
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/24 • 28 days after enrollment
|
12.5%
3/24 • Number of events 3 • 28 days after enrollment
|
|
Renal and urinary disorders
Elevated liver function test
|
0.00%
0/24 • 28 days after enrollment
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
|
Blood and lymphatic system disorders
Hematuria
|
0.00%
0/24 • 28 days after enrollment
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
|
Blood and lymphatic system disorders
Hemolysis
|
0.00%
0/24 • 28 days after enrollment
|
8.3%
2/24 • Number of events 2 • 28 days after enrollment
|
|
General disorders
Pain
|
0.00%
0/24 • 28 days after enrollment
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
|
Metabolism and nutrition disorders
Vitamin B1 deficiency
|
0.00%
0/24 • 28 days after enrollment
|
4.2%
1/24 • Number of events 1 • 28 days after enrollment
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/24 • 28 days after enrollment
|
8.3%
2/24 • Number of events 2 • 28 days after enrollment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place