Overnight auto-adjusting continuous airway pressure + standard care compared with standard care alone in the prevention of morbidity in sickle cell disease phase II (POMS2b): study protocol for a randomised controlled trial

Abstract

BackgroundIn 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 compounded by obstructive sleep apnoea (OSA). In the general population OSA is treated with continuous positive airways pressure (CPAP). 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 individuals with HbSS to determine whether the intervention improves attention and processing speed, brain structure, pain and quality of life.Methods/DesignEligibility criteria include: ability to provide informed consent; age > 8 years; diagnosis of HbSS; and mean overnight saturation of < 90% for < 30% of the night (i.e. not meeting current criteria for overnight oxygen therapy). Key exclusion criteria are: overnight respiratory support; respiratory or decompensated cardiac failure; chronic transfusion; or contraindications to APAP therapy or magnetic resonance imaging (MRI).Sixty individuals with HbSS (30 children and 30 adults) will be randomised to standard care + APAP or standard care alone for six months. Minimisation factors are: age group (8–11, 12–15, 16–22 and > 23 years); silent infarction on MRI; minimum overnight oxygen saturation > 90% or < 90%; and hydroxyurea use.For APAP individuals, the intervention is administered at home. Adherence and effectiveness are recorded using software documenting hours of use each night and overnight oximetry. Participant support in terms of appropriate facemask and facilitating adherence are provided by an unblinded sleep physiologist.The primary outcome is change in the cancellation subtest from the Wechsler scales. Secondary outcomes include general cognitive functioning, quantitative brain MRI, blood and urine chemistry, quality of life and daily pain via a smartphone App (GoMedSolutions, Inc) and, where possible MRI heart, echocardiography, and 6-min walk. These outcomes will be assessed at baseline and after six months of treatment by assessors blind to treatment assignment.DiscussionAltering oxygen saturation in HbSS may lead to bone marrow suppression. This risk will be reduced by monitoring full blood counts at baseline, two weeks, three months and six months, providing treatment as appropriate and reporting as safety events.Trial registrationISRCTN46012373. Registered on 10 July 2015.Protocol Version: 6.0 Date: 24th December 2015Sponsor: University Hospital Southampton. Sponsor’s protocol code: RHMCHIOT53

White matter integrity and processing speed in sickle cell anemia

“…Overnight respiratory support appears to be safe and viable in children with SCA and is a treatment option that may hold promise. 23 …”

“…Patients were aged 8 to 38 years and enrolled in 2 studies at University College London: the Sleep and Asthma Cohort follow-up study (SAC-III) 22 and Prevention of Morbidity in SCA 2b (POMS) 23 baseline investigation. Controls were healthy siblings of patients recruited to either study with no history of neurologic or psychiatric conditions.…”

Index of Pain Experience in Sickle Cell Anaemia (IPESCA): development from daily pain diaries and initial findings from use with children and adults with sickle cell anaemia

“…The sample included 61 children and adults screened for the Prevention of Morbidity in Sickle Cell Anaemia (POMS) phase‐II randomised controlled trial (Howard et al , ). At screening visit, patients completed a paper pain diary for 14 consecutive days, which included shading locations of pain on a body map, circling words to describe their pain and choosing a 0–10 numerical rating of pain intensity.…”

“…American Journal of Hematology, 92, 885-891. Rumi, E., Boveri, E., Bellini, M., Pietra, D., Ferretti, V.V., Sant'Antonio, E., Cavalloni, C., Casetti, I.C., Roncoroni, E., Ciboddo, M., Benvenuti, P., Landini, B., Fugazza, E., Troletti, D., Astori, C. & Cazzola, M. (2017) (Howard et al, 2018). At screening visit, patients completed a paper pain diary for 14 consecutive days, which included shading locations of pain on a body map, circling words to describe their pain and choosing a 0-10 numerical rating of pain intensity.…”

Prevention of Morbidity in Sickle Cell Disease (POMS2a)—overnight auto-adjusting continuous positive airway pressure compared with nocturnal oxygen therapy: a randomised crossover pilot study examining patient preference and safety in adults and children

“…Auto-adjusting continuous positive airway pressure (APAP), which increases airway pressure when the patient’s airway obstructs, appears to improve attention/processing speed, measured as cancellation, and reduce pain episodes in children with SCA [12]. CPAP has been used peri-operatively in adults with sickle cell disease (SCD) [13] but, although the results of a Phase II study are awaited [14], there are as yet no published data on longer term use in adults. However, there is observational evidence that nocturnal oxygen therapy (NOT), used for a period of at least 6 months in adults with SCA and severe nocturnal hypoxia, is safe and easy to use [11].…”