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. Author manuscript; available in PMC: 2011 Nov 14.
Published in final edited form as: Lancet. 2011 May 14;377(9778):1663–1672. doi: 10.1016/S0140-6736(11)60355-3

Table 3.

Secondary Endpoint Results

Hydroxyurea
Placebo
Difference1 (95% CI) p-value*
no. N^ % no. N^ %
Splenic Function
Pitted Cell Counts ≥3·5% at Exit 41 86 48 51 82 62 −15% (−29%, 0·4%) 0·06
Pitted Cell Counts ≥3·5% at Exit (Compared with Baseline) 0·03
 Better (number ≥3·5%→<3·5%) 9 85 11 3 82 4 7% (−8%, 22%)#
 Same 63 74 55 67 7% (−7%, 21%)
 Worse (number <3·5%→≥3·5%) 13 15 24 29 −14% (−26%, −2%)
Howell Jolly Body Counts ≥300/106 RBC at Exit 54 83 65 67 85 79 −14% (−28%, 1%) 0·06
Howell Jolly Body Counts ≥300/106 RBC at Exit (Compared with Baseline) 0·005
 Better (number ≥300→<300) 1 76 1 0 82 0 1% (−14%, 17%)#
 Same 59 78 47 57 20% (6%, 35%)
 Worse (number <300→≥300) 16 21 35 43 −22% (−36%, −8%)
N^ Entry Exit %Diff N^ Entry Exit %Diff Difference2 (95%CI) p-value§
Howell-Jolly Bodies -- per 106 RBC 76 663 1360 106 82 495 1470 197 −274 (−538, −10) 0·04
Pitted Cells -- % 85 4·3 5·7 32 82 4·6 8·4 84 −2·5 (−4·7, −0·2) 0·04
Spleen:Liver Ratio of Counts (400K) 84 0·36 0·28 −20 79 0·38 0·20 −46 0·10 (0·01, 0·19) 0·03
Spleen Volume -- cm3 80 110 157 43 80 98 132 34 14 (−14, 42) 0·33
Renal Function
Creatinine -- mg/dL 69 0·2 0·3 10 78 0·2 0·2 12 −0·005 (−0·04, 0·03) 0·77
Schwartz GFR -- mL/min/1·73m2 69 192 218 13 73 196 229 17 −8 (−37, 21) 0·60
Cystatin C -- ug/mL 39 0·91 0·92 1 48 0·91 0·89 −3 0·03 (−0·05, 0·11) 0·42
Urine Osmolality -- mOsm/kg H2O 81 384 494 29 84 400 454 13 57 (3, 110) 0·04
Urine pH 86 6·5 6·3 −2 82 6·6 6·3 −4 0·15 (−0·22, 0·51) 0·43
Urine Specific Gravity 86 1·010 1·012 0 82 1·012 1·011 0 0·002 (0·0004, 0·004) 0·02
Total Kidney Volume -- cm3 80 61 91 48 79 58 97 67 −9 (−16, −2) 0·01
Central Nervous System
TCD Velocity (TAMM)-- cm/sec 79 126 146 16 79 118 150 27 −12 (−18, −6) <0·001
Bayley Mental MDI 85 97 97 1 80 97 94 −3 3 (−2, 8) 0·22
Bayley Motor PDI 85 97 101 5 79 97 99 2 2 (−3, 7) 0·37
Growth
Height -- cm 87 75·9 96·2 27 82 75·7 96·2 27 −0·2 (−1·0, 0·6) 0·62
Weight -- kg 87 9·7 14·5 50 85 9·6 14·3 49 0·1 (−0·2, 0·4) 0·53
Head Circumference -- cm 85 46·9 50·3 7 82 46·8 50·3 8 −0·2 (−0·6, 0·2) 0·44
Pulmonary
O2 Saturation -- % 86 99 99 0 86 99 98 −1 0·6 (−0·04, 1·2) 0·07
Laboratory Results
Haemoglobin -- g/dL 79 8·9 9·1 3 79 9·2 8·6 −7 0·9 (0·5, 1·3) <0·001
HbF -- % 80 25·6 22·4 −13 78 27·1 17·1 −37 6·7 (4·8, 8·7) <0·001
MCV -- fL 79 80·2 92·2 15 79 80·0 86·2 8 5·7 (4·0, 7·5) <0·001
WBC -- x103/mm3 79 14·4 10·6 −27 79 14·3 13·9 −3 −3·4 (−6·0, −0·9) 0·008
Absolute Neutrophil Count -- x103/mm3 69 4·9 4·5 −7 72 4·2 5·6 33 −1·7 (−2·9, −0·5) 0·005
Platelet Count -- x103/mm3 78 374 351 −6 79 404 415 3 −33 (−87, 21) 0·23
Absolute Reticulocyte Count -- x103/mm3 79 286 227 −21 79 265 277 5 −71 (−107, −35) <0·001
Reticulocytes -- % 80 9·2 7·9 −14 79 8·2 10·0 22 −3·1 (−4·5, −1·8) <0·001
Total Bilirubin -- mg/dL 81 1·6 1·8 16 85 1·6 2·3 46 −0·5 (−0·8, −0·1) 0·01
^

N: Total number of subjects evaluated for each endpoint. N differs from the number reported in Table 1 because only entry values that are paired with exit values (from the same subject) are included.

1

Difference of (Exit – Entry) percentages in Hydroxyurea and Placebo groups

*

p-value is calculated using Fisher’s exact test under the assumption that proportions are equal in the Hydroxyurea and Placebo groups.

#

Confidence interval is determined using the Exact test calculation from a non-central hypergeometric distribution.

2

Difference of (Exit – Entry) differences in Hydroxyurea and Placebo groups

§

p-value is calculated using Student’s t-test comparing the exit versus entry differences in means between the Hydroxyurea and Placebo groups.

TCD = Transcranial Doppler ultrasound

TAMM = Time-averaged mean maximum (velocity)

MDI = Mental Developmental Index

PDI = Performance Developmental Index