Background
Methods
Design and treatment protocol
Study population
Screening procedure
Outcome measures
Study procedures
Consent
Randomization
Sample size
Clinical monitoring and study assessments
Further management
Statistical analysis
Results
Study patients
Arm A: Tx20 | Arm B: Tx30 | Total | |
---|---|---|---|
20 ml/kg | 30 ml/kg | ||
Variable | (Number = 82) | (Number = 78) | (Number = 160) |
Demographic and anthropometric characteristics
| |||
Age months median (IQR) | 36 (19 to 54) | 31 (11 to 48) | 36 (13 to 53) |
Female sex – n/ total n (%) | 41/82 (50) | 40/77 (52) | 81/159 (51) |
Mid-upper arm Circumference ≤11.5 cm – n/total n (%) | 1/80 (1) | 3/78 (4) | 4/158 (3) |
Weight kg - median (IQR) | 13 (9-16) | 11 (8-15) | 12 (9-15) |
Findings at presentation
| |||
Axillary temperature | |||
>37.5°C – n/total n (%) | 39/81 (48) | 37/78 (47) | 76/159 (48) |
<36°C (Hypothermia) – n/total n (%) | 3/81 (4) | 4/78 (5) | 7/159 (4) |
Oxygen saturation <90% - n/total n (%) | 9/78 (12) | 9/78 (12) | 18/156 (12) |
Moderate hypotension - n (%) | 5 (6) | 6 (8) | 11 (7) |
Dehydration - n (%) | 6 (7) | 6 (8) | 12 (8) |
Severe pallor (lips, gums, or inner eyelids) - n (%) | 81 (99) | 76 (97) | 157 (98) |
Consciousness level – n (%) | |||
Total n | 81 | 78 | 159 |
Alert | 51 (63) | 56 (72) | 107 (67) |
Prostration | 29 (36) | 20 (26) | 49 (31) |
Coma | 1 (1) | 2 (3) | 3 (2) |
Convulsions during this illness - n (%) | 6 (7) | 13 (17) | 19 (12) |
Hemoglobinuria (dark urine) - n (%) | 29 (35) | 26 (33) | 55 (34) |
Jaundice visible to clinician - n (%) | 43 (52) | 44 (56) | 87 (54) |
Respiratory rate breaths/minute | |||
mean ± sd | 47 ± 15 | 47 ± 13 | 47 ± 14 |
respiratory distress – n (%) | 41 (50) | 43 (55) | 84 (53) |
Heart rate beats/minute | |||
median (IQR) | 153 (136 to 173) | 156 (142 to 168) | 155 (139 to 170) |
Bradycardia (<80) - n (%) | 1 (1) | 0 (0) | 1(1) |
Severe tachycardia - n (%)a
| 30 (37) | 26 (33) | 56 (35) |
Hepatomegaly – n/total n (%) | 32/82 (39) | 25/77 (32) | 57/159 (36) |
Laboratory assessment
| |||
Hemoglobin - n (%) | |||
Median (IQR) | 4.2 (3.0 to 4.8) | 4.3 (3.3 to 4.9) | 4.2 (3.1 to 4.9) |
<4 g/dl | 37 (45) | 36 (46) | 73 (46) |
Glucose – n/ total n (%) | |||
<2.5 mmol/liter (45 mg/dl) | 2/82 (2) | 0/75 (0) | 2/157 (1) |
<3.0 mmol/liter (54 mg/dl) | 2/82 (2) | 0/75 (0) | 2/157 (1) |
Lactate ≥5 mmol/liter – n/total n (%) | 23/82 (28) | 26/76 (34) | 49/158 (31) |
Positive for HIV antibody - n/ total n (%) | 1/39 (3) | 0/38 (0) | 1/77 (1) |
Positive for malaria parasitemia - n (%) | |||
Negative on all tests done | 33 (40) | 32 (41) | 65(41) |
RDT positive, slide negative/unknown | 13 (16) | 15 (19) | 28 (18) |
RDT negative/unknown, slide positive | 4 (5) | 3 (4) | 7 (4) |
RDT positive, slide positive | 32 (39) | 28 (36) | 60 (38) |
Genotypes
| |||
Sickle cell– n (%) | |||
AA (normal) | 63 (77) | 57 (73) | 120 (75) |
AS (sickle cell trait) | 2 (2) | 6 (8) | 8 (5) |
SS (sickle cell anemia) | 17 (21) | 15 (19) | 32 (20) |
Alpha thalassemia – n (%) | |||
Normal | 45 (60) | 48 (65) | 93 (62) |
Heterozygote | 24 (32) | 24 (32) | 48 (32) |
Homozygote | 6 (8) | 2 (3) | 8 (5) |
G6PD deficiency – n (%) | |||
Normal | 56 (77) | 55 (79) | 111 (78) |
Heterozygote/Hemizygoteb
| 8 (11) | 7 (10) | 15 (10) |
Homozygote | 9 (12) | 8 (11) | 17 (12) |
Transfusions administered
Arm A: 20 ml/kg (Number = 82) | Arm B: 30 ml/kg (Number = 78) |
Pvalue | |
---|---|---|---|
Volume of initial transfusiona (ml/kg) – median (IQR) | 20 (20 to 20) | 30 (30 to 30) | <0.0001 |
Rate of initial transfusiona (ml/kg/hr) – median (IQR) | 5.7 (4.9 to 6.7) | 7.6 (6.1 to 8.4) | <0.0001 |
Time to initial transfusion (minutes) – median (IQR) | 95 (75 to 128) | 103 (75 to 130) | 0.74 |
Total volume tranfused 0 to 48 hours (ml/kg) – median (IQR) | 20 (20 to 20) | 30 (30 to 30) | <0.0001 |
Number of transfusionsb per child 0 to 48 hours, number (%) | 0.23 | ||
1 | 67 (82) | 69 (88) | |
2 | 14 (17) | 8 (10) | |
3 | 0 (0) | 1 (1) | |
4 | 1 (1) | 0(0) | |
Number of children with a transfusion after 48 hours | 2 | 1 |
Outcomes
End point | Arm A: 20 ml/kg (N = 82) | Arm B: 30 ml/kg (N = 78) | Risk ratio (95% CI) |
Pvalue |
---|---|---|---|---|
Time to correction of severe anemia (by 24 hours) - number (%) | 61 (74) | 70 (90) | 1.54a (1.09,2.18) | 0.01 |
Children meeting the criteria for additional transfusion - number (%) | 12 (15) | 4(5) | 0.35 (0.12, 1.04) | 0.06 |
SAE – number (%) | 6 (7) | 2 (3) | 0.35 (0.07, 1.68) | 0.28 |
Died before 48 hours – number (%) | 4 (5) | 0 (0) | 0.12 | |
Died before 28 days post-admission – number (%) | 6 (7) | 1 (1) | 0.18 (0.02, 1.42) | 0.12 |
Severe anemia or mortality at 28 days – number/total nb (%) | 9/76 (12) | 4/72 (6) | 0.47 (0.15, 1.46) | 0.25 |
Serious adverse events
SAE | Arm A: 20 ml/kg (Number = 82) | Arm B: 30 ml/kg (Number = 78) | Total |
---|---|---|---|
Clinician defined SAEs | |||
Allergic reaction/transfusion reaction | 0 | 1a
| 1 |
Deaths | |||
Cardio respiratory arrest | 1 | 0 | 1 |
Respiratory arrest | 1 | 0 | 1 |
Multiple organ failure | 0 | 1b
| 1 |
Other deaths | 4 | 0 | 4 |
Total
| 6 | 2 | 8 |
Adjudication by endpoint committee
| |||
Fatal events relationship to transfusion
c
| |||
Definitely | 0 | - | |
Probably | 0 | - | |
Possibly | 3 | - | |
Not related | 3 | 1b
| |
unknown | 0 | - |