Prevention of morbidity in sickle cell disease phase II (Improvement of Pain and Quality of Life in Children with Sickle Cell Disease with Auto-adjusting Continuous Positive Airways Pressure: Phase II) (POMS 2b pediatric cohort) | oneSCDvoice
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abstracts & posters

Prevention of morbidity in sickle cell disease phase II (Improvement of Pain and Quality of Life in Children with Sickle Cell Disease with Auto-adjusting Continuous Positive Airways Pressure: Phase II) (POMS 2b pediatric cohort)

key information

source: American Society of Hematology

year: 2017

authors: Baba Inusa, Jo Howard, Subarna Chakravorty, Maria Pelidis, Swee Lay Thein, Fenella J Kirkham

summary/abstract:

In addition to pain, sickle cell anaemia (HbSS) complications include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time oxygen saturation. These effects can be compounded by obstructive sleep apnoea (OSA). Continuous Positive Airways Pressure (CPAP) is an accepted treatment for OSA in the general population. However, supplementary oxygen therapy in SCA may lead to bone marrow suppression. The aim of this single-blind, randomised, controlled phase II trial is to compare Auto-adjusting CPAP (APAP) with standard care to standard care alone in subjects with HbSS to determine whether the intervention is safe and improves attention and processing speed and brain structure.

Methods: Eligibility criteria included ability to provide informed consent, age >8 and <16 years, diagnosis of HbSS and mean overnight saturation of <90% for <30% of the night. Key exclusion criteria were overnight respiratory support, respiratory or decompensated cardiac failure, chronic transfusion or contra-indications to APAP therapy or MRI. Minimisation factors were age group (8-11, 12-15), silent infarction on MRI, minimum overnight oxygen saturation > or < 90%, and hydroxyurea (HU) use. APAP adherence was defined as using APAP for an average of 4 hours a night for >50% of the time and was recorded using software documenting hours of use each night. Participant support in terms of appropriate facemask and facilitating adherence were provided by an unblinded sleep physiologist. Full blood counts were obtained at baseline, 2 weeks, 3 months and 6 months. Data were analysed by intention-to-treat. The primary outcome is change in the cancellation subtest from the Wechsler scales, and secondary outcomes include general cognitive functioning, assessed at baseline and after 6 months of treatment by assessors blind to treatment assignment. Analysis of Covariance (ANCOVA) models, adjusted for minimisation factors, were used to calculate least-square mean changes from baseline to 6 months.

Results: 30 children with HbSS were randomised to standard care + APAP (n=15) or standard care alone (n=15) for 6 months. One child in the standard care arm withdrew after 6 weeks, and 8 children in the APAP arm were not adherent to treatment. There was no difference in hemoglobin change between the arms, but hydroxyurea use was associated with an increase in haemoglobin (p=0.01). Increase in cancellation score was numerically greater in the APAP arm (mean 1.46, SE 0.59 vs 1.01, SE 0.61) but this was not significant (mean difference 0.44, 95% CI: -1.42; 2.31; p=0.626). Increase in cancellation score was greater (mean 2.63; 95%CI: 0.95, 4.30) in those whose adherence was in the highest quartile (> 2.4 hours/night) compared with the other 3 quartiles (mean 0.71, 95%CI: -0.32, 1.75; mean difference 1.91, 95%CI: -0.06, 3.88; p=0.057). In subjects assigned to APAP, cancellation scores were significantly higher with hydroxyurea use (p=0.01). There were 7 subjects with serious adverse events in the placebo group, compared to 3 in the APAP group, all related to SCD pain. There was no evidence of decline in haemoglobin in either group.

organisation: Guy's and St Thomas' NHS Trust, United Kingdom; Evelina Children's Hospital, United Kingdom; King's college hospital, United Kingdom; The National Institutes of Health, Bethesda, MD; UCL GOSH Institute of Child Health, United Kingdom

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