Outcomes parameters and measurement
| First primary outcome | |
| Difference in the global VAS (VAS 0 to 10) | Difference between the global VAS score—H0 (immediately before first HBOT session) and the global VAS score—H6 (4 hours after first HBOT session). Pain network: Réseau douleur à Genève aux HUG - HUG. |
| Second primary outcome | |
| Composite outcome: Number of patients with a VAS >4 and/or a morphine dose within 4 hours after the HBOT session >1 mg/hour IV morphine equivalent in addition to the usual outpatient dose. | This evaluation will be made 4 hours after each HBOT session. The dose will be calculated based on PCA morphine usage data. All additional forms of morphine administered will be included in this calculation. An equivalent of this morphine will be calculated according to the recommendations of the Pain Network. |
| Secondary outcomes | |
| Length of stay | In the different acute wards (in days), starting from admission to the ED until discharge or transfer to a rehabilitation facility |
| CPS ranges from 0 to 3 points in 7 body sites (the 4 limbs, ribs and sternum, head, and spine and pelvis). | Difference between the global CPS score—H0 (immediately before first HBOT session) and the global CPS score—H6 (4 hours after first HBOT session). Same measurements for second and third sessions. |
| Number of patients relieved at H6 and H24 | Defined by a reduction of VAS score >30% with doses of level 3 painkillers inferior or equal to compared with H049 |
| Frequency of patients with VOC terminated at each visit | VOC is terminated when VAS <2, in the absence of level 3 painkillers |
| Duration of VOC since inclusion (in hours) | A VOC is considered terminated when at least 3 of the following four criteria are met: absence of fever for 8 hours; absence of pain progression and requirement of intravenous infusion of opioid analgesics for the last 8 hours; pain-free mobilisation; or absence of spontaneous pain with a CPS of 1 or less. The success rate will be defined as the percentage of VOC terminated without recourse to transfusion and or the occurrence of complications.50 |
| Indications and use of transfusions or transfusion exchanges | |
| The occurrence of complications during hospitalisation | |
| Vital signs | Heart rate, blood pressure and percutaneous oxygen saturation will be measured before and after each HBOT session |
| Relevant biological markers of sickle cell crisis | CRP (C-reactive protein), LDH (Lactate DesHydrogenase), haemoglobin and reticulocytes levels, leucocytes, when carried out at inclusion and again at H24 |
| Patient satisfaction and impression questionnaire | Questions about :
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| The Patient Global Impression of Change scale (PGIC) | Assessed as recommended by IMMPACT for use in chronic pain clinical trials as a core outcome measure of global improvement with treatment49 |
| Evaluation of VOC recurrences requiring hospitalisation | A new episode of VOC will be defined by the recurrence of painful spell after a free interval >24 hours pain-free or with usual pain level |
| A medico-economic analysis | Based on the actual expenditure in the intervention and control groups |
| Ancillary study ‘Biobank’ | Blood samples to measure these biomarkers will be taken immediately before and after the first HBOT session, with a third sample being taken at 24 to 36 hours after the beginning of the HBOT session or just before discharge if less than 24 hours. Consequences of oxidative stress on lipids: Dosage of plasma malondialdehyde, measurement of lipid peroxidation, dosage of Thiols Barbituric Acid Reactive Species Oxidative stress on proteins (Oxyblot): Measurement of advanced glycation products, nitrosation products and protein glutathione formation Serum markers of inflammation: Dosage of pro and anti-inflammatory cytokines (IL2-IL6, IL10, IL1-β, TNFα, IL12) Adhesion proteins: ICAM-1, VCAM-1, glycocalix Tissue ischaemia: ischaemia modified albumin |
| Safety outcomes | Any side effects will be systematically documented both during and/or following each HBOT session by the HMU or ward team. Details will include date, precise time, duration and a detailed account of the event as well as the action and effect of the action taken. The probability of the HBOT session being accountable for the side effect and severity will be rated according to the usual grading: mild (tolerable), moderate (interferes with daily activity) or severe (daily activities impossible). Any serious adverse event must be reported to the principal investigator within 24 hours. |
CPS, Categorical Pain Score; CRP, C-reactive protein; ED, emergency department; HBOT, hyperbaric oxygen therapy; HMU, Hyperbaric Medicine Unit; IV, intravenous; LDH, Lactate DesHydrogenase; PCA, Patient Controlled Analgesia; VAS, Visual Analogue Scale; VOC, vaso-occlusive crisis.