Background
Methods
Study area
Study design
Study population
Randomization and blinding
Treatment
Patient withdrawals
Procedures
Study end-points
Ethical considerations
Statistical analysis
Results
Characteristic | Treatment arm |
P value | |
---|---|---|---|
AL (N = 110) | AL + PQ (N = 110) | ||
Female sex, n (%) | 55 (50) | 55 (50) | |
Age (years), median (range) | 10 (1–84) | 9 (1–75) | 0.392a
|
Body weight(kg), mean (SD) | 34.3 (19.6) | 30.7 (17.1) | 0.145b
|
Body temperature(0C), mean (SD) | 38.3 (1.3) | 38.3 (1.1) | 0.977b
|
Haemoglobin concentration (g/dl), mean (SD) | 11.4 (1.6) | 11.1 (1.5) | 0.097b
|
Geometric mean asexual parasite density/µl, (range) | 8384 (240–389,045) | 8327 (240–288,403) | 0.982b
|
Fever (> 37.5 °C) at inclusion, n (%) | 80 (72.7) | 88 (80.0) | 0.204c
|
G6PD status
PhenotypicG6PD status
Genotypic G6PD status
Treatment arm | Sex | ||||
---|---|---|---|---|---|
Male | Female | ||||
Hemizygous | Wild-type/normal | Homozygous | Heterozygous | Wild-type/normal | |
AL | 10 (18.2 %) | 45 (81.8 %) | 1 (1.8 %) | 10 (18.2 %) | 44 (80.0 %) |
AL + PQ | 5 (9.1 %) | 50 (90.9 %) | 4 (7.3 %) | 12 (21.8 %) | 39 (70.9 %) |
Total | 15 (13.6 %) | 95 (86.4 %) | 5 (4.5 %) | 22 (20.0 %) | 83 (75.5 %) |
Phenotypic and genotypic G6PD test agreement
Genotype results | Phenotype results | N/N (%) |
---|---|---|
Male hemizygous | Deficient | 9/14 (64.3) |
Normal | 5/14 (35.7) | |
Male wild-type/normal | Deficient | 12/93 (12.9) |
Normal | 81/93 (87.1) | |
Female homozygous | Deficient | 0/5 (0) |
Normal | 5/5 (100) | |
Female heterozygous | Deficient | 4/22 (18.2) |
Normal | 18/22 (81.8) | |
Female wild-type/normal | Deficient | 8/83 (9.6) |
Normal | 75/83 (90.4) |
Hb reduction between days 0 and 7 by phenotypic or genotypic G6PD status and treatment arm
Absolute Hb reduction
Characteristic | Treatment arm | |
---|---|---|
AL | AL + PQ | |
A: Mean absolute and relative Hb reduction by phenotypic G6PD status | ||
Mean absolute Hb reduction (g/dL) (95 % CI)
| ||
G6PD normal | 0.83 (0.57–1.10) | 0.81 (0.59–1.02) |
G6PD deficient | 0.88 (0.32–1.45) | 1.16 (0.67–1.66) |
P value | 0.87 | 0.23 |
Mean relative Hb reduction (%) (95 % CI)
| ||
G6PD normal | 6.4 (4.29–8.56) | 7.2 (5.04–9.35) |
G6PD deficient | 7.8 (4.23–11.36) | 7.9 (4.58–11.18) |
P value | 0.71 | 0.16 |
B: Mean absolute and relative Hb reduction by genotypic G6PD status | ||
Mean absolute Hb reduction (g/dL) (95 % CI)
| ||
G6PD wild-type/normal | 0.82 (0.56–1.1) | 0.74 (0.52–0.95) |
G6PD heterozygous | 1.68 (0.87–2.51) | 1.27 (0.56–1.99) |
P value | 0.048 | 0.09 |
G6PD hemizygous/homozygous | 0.35 (−0.36–1.1) | 1.48 (0.59–2.37) |
P value | 0.21 | 0.047 |
Mean relative Hb reduction (%) (95 % CI)
| ||
G6PD wild-type/normal | 6.8 (4.67–8.96) | 6.2 (4.25–8.17) |
G6PD heterozygous | 14.3 (7.02–21.55) | 10.9 (5.10–16.87) |
P value | 0.045 | 0.09 |
G6PD hemizygous/homozygous | 2.7 (4.22–9.68) | 12.6 (6.0–19.25) |
P value | 0.21 | 0.059 |
Relative Hb reduction
Treatment arm | Variable | Coefficient | 95 % CI |
P value |
---|---|---|---|---|
AL | Heterozygous | −6.61 | −13.75 to 0.53 | 0.124 |
Hemi/Homozygous | 4.29 | −1.87 to 10.45 | 0.407 | |
AL + PQ | Heterozygous | −3.97 | −8.98 to 1.03 | 0.095 |
Hemi/Homozygous | −6.22 | −12.22 to −0.22 | 0.068 |
Adverse events
Adverse event | Treatment arm | |||||
---|---|---|---|---|---|---|
AL | AL + PQ | |||||
Normal | Deficient | Normal | Deficient | |||
A: Distribution of adverse events by phenotypic G6PD status
| ||||||
Abdominal pain | 6 (10.5 %) | 1 (7.1 %) | 6 (10.7 %) | 1 (11.1 %) | ||
Blurred vision | 1 (1.8 %) | 0 | 0 | 0 | ||
Cold sores | 2 (3.5 %) | 1 (7.1 %) | 4 (7.1 %) | 0 | ||
Diarrhoea | 3 (5.3 %) | 1 (7.1 %) | 2 (3.6 %) | 1 (11.1 %) | ||
Dizziness | 2 (3.5 %) | 0 | 1 (1.8 %) | 0 | ||
Fever | 21 (36.8 %) | 3 (21.4 %) | 14 (25.0 %) | 2 (22.2 %) | ||
Headache | 7 (12.3 %) | 1 (7.1 %) | 5 (8.9 %) | 0 | ||
Hb fall ≥ 25 % | 5 (8.8 %) | 2 (14.3 %) | 5 (8.9 %) | 0 | ||
Acute haemolytic anaemia | 1 (1.8 %) | 2 (14.3 %) | 2 (3.6 %) | 1 (11.1 %) | ||
Haemoglobinuria | 1 (1.8 %) | 2 (14.3 %) | 10 (17.9 %) | 4 (44.4 %) | ||
Nausea | 2 (3.5 %) | 0 | 0 | 0 | ||
Rashes | 0 | 0 | 1 (1.8 %) | 0 | ||
Vomiting | 5 (8.8 %) | 1 (7.1 %) | 6 (10.7 %) | 0 | ||
Weakness | 1 (1.8 %) | 0 | 0 | 0 | ||
Total | 57 (100 %) | 14 (100 %) | 56 (100 %) | 9 (100 %) |
AL | AL + PQ | |||||
---|---|---|---|---|---|---|
Wild-type/normal | Heterozygous | Hemizygous/homozygous | Wild-type/normal | Heterozygous | Hemizygous/homozygous | |
B: Distribution of adverse events by genotypic G6PD status
| ||||||
Abdominal pain | 7 (11.3 %) | 0 | 0 | 4 (8.0 %) | 4 (44.0 %) | 0 |
Blurred vision | 1 (1.6 %) | 0 | 0 | 0 | 0 | 0 |
Cold sores | 3 (4.8 %) | 0 | 0 | 4 (8.0 %) | 0 | 0 |
Diarrhoea | 2 (3.2 %) | 1 (12.5 %) | 1 (100 %) | 3 (6.0 %) | 0 | 0 |
Dizziness | 1 (1.6 %) | 1 (12.5 %) | 0 | 0 | 1 (10.0 %) | 0 |
Fever | 21(33.9 %) | 3 (37.5 %) | 0 | 10 (20.0 %) | 3 (30.0 %) | 3 (50.0 %) |
Headache | 8 (12.9 %) | 0 | 0 | 4 (8.0 %) | 0 | 1 (16.7 %) |
Hb fall ≥ 25 % | 5 (8.1 %) | 2 (25.0 %) | 0 | 5 (10.0 %) | 0 | 0 |
Acute haemolytic anaemia | 3 (4.8 %) | 0 | 0 | 2 (4.0 %) | 1 (10.0 %) | 0 |
Haemoglobinuria | 3 (4.8 %) | 0 | 0 | 12 (24.0 %) | 1 (10.0 %) | 1 (16.7 %) |
Nausea | 1 (1.6 %) | 1 (12.5 %) | 0 | 0 | 0 | 0 |
Rashes | 0 | 0 | 0 | 1 (2.0 %) | 0 | 0 |
Vomiting | 6 (9.7 %) | 0 | 0 | 5 (10.0 %) | 0 | 1 (16.7 %) |
Weakness | 1 (1.6 %) | 0 | 0 | 0 | 0 | 0 |
Total | 62 (100 %) | 8 (100 %) | 1 (100 %) | 50 (100 %) | 10 (100 %) | 6 (100 %) |