NCT03976180 High-flow Oxygen for Vaso-occlusive Pain Crisis
| NCT ID | NCT03976180 |
| Status | Recruiting |
| Phase | — |
| Sponsor | Assistance Publique - Hôpitaux de Paris |
| Condition | Sickle Cell Disease |
| Study Type | INTERVENTIONAL |
| Enrollment | 350 participants |
| Start Date | 2020-04-27 |
| Primary Completion | 2025-11-27 |
Eligibility & Interventions
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
This trial targets 350 participants in total. It began in 2020-04-27 with a primary completion date of 2025-11-27.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive pain crisis (VOC), which may evolve to acute chest syndrome (ACS), the most common cause of death among adult patients with SCD. Currently, there is no safe and effective treatment to abort VOC or prevent secondary ACS. Management of VOC mostly involve a symptomatic approach including hydration, analgesics, transfusion, and incentive spirometry, which was investigated in a very limited number of patients (\<30). The polymerisation of HbS is one major feature in the pathogenesis of vaso-occlusion. Among factors determining the rate and extent of HbS polymer formation, the hypoxic stimulus is one of the most potent and readily alterable. Current guidelines recommend oxygen therapy in patients with VOC in order to maintain a target oxygen saturation of 95%. Low-flow nasal oxygen (LFNO) is routinely used to achieve this normoxia approach, particularly in patients at risk of secondary ACS because they may experience acute desaturation. In contrast, various case series suggest a potential beneficial role of intensified oxygen therapy targeting hyperoxia for the management of VOC, particularly with the use of hyperbaric oxygen, but the latter is difficult to implement in routine clinical practice. A recent high-flow nasal oxygen (HFNO) technology allows the delivery of humidified gas at high fraction of inspired oxygen (FiO2) through nasal cannula. The FiO2 can be adjusted up to 100% (allowing hyperoxia that may reverse sickling) and the flow can be increased up to 60 L/min (which generates positive airway pressure and dead space flushing, that may prevent evolution of VOC towards ACS by alleviating atelectasis and opioid-induced hypercapnia). In patients with acute respiratory failure, HFNO has been shown to improve patient's comfort, oxygenation, and survival as compared to standard oxygen or non-invasive ventilation. The aim of the present study is to test the efficacy and safety of HFNO for the management of VOC and prevention of secondary ACS. The investigators will use a multi-arm multi-stage (MAMS) design to achieve these goals. HFNO will be delivered through AIRVO 2 (Fisher and Paykel Healthcare, New Zealand), a device that incorporates a turbine allowing its use in hospital wards.
Eligibility Criteria
Inclusion Criteria: * Age ≥ 18 years; * Patient with major sickle cell disease syndrome (SS, SC, Sβ0 or Sβ+); * VOC as defined by acute pain or tenderness, affecting at least one part of the body, including limbs, ribs, sternum, head (skull), spine, and/or pelvis, that requires opioids and is not attributable to other causes; * Intermediate-to-high risk for secondary ACS derived from the PRESEV score (Bartolucci et al, EBioMedicine 2016) as follows: a reticulocyte count \>216 G/L OR at least two of the followings : i) spine and/or pelvis CPS \>1; ii) leucocyte count \>11G/L; iii) hemoglobin ≤ 9 g/dL; in case of long-term treatment by hydroxyurea, only one of the above mentioned criteria will be needed, given its effects on hemoglobin, leucocyte and reticulocytes counts; * Informed consent; * Patient affiliated to social security Exclusion Criteria: The presence at inclusion of a primary ACS. Primary ACS is defined by the combination at time of randomization of a clinical sign \[chest pain or auscultatory abnormality (crepitants and/or bronchial breathing)\] with a new pulmonary infiltrate (on chest film, thoracic scan, or lung ultrasound); * VOC with need of parenteral opioids lasting longer than 72 hours at time of inclusion; * Known pregnancy or current lactation; Women of child bearing potential will be tested for pregnancy before inclusion; * Known cerebral vasculopathy or past medical history of stroke, due to Moya Moya or persisting visible macrovessel stenosis/occlusion; * Known ischemic heart disease or typical chest angina; * Patient who is currently enrolled in other investigational drug study; * Known legal incapacity, * Prisoners or subjects who are involuntarily incarcerated * Anatomical factors precluding placement of a nasal cannula
Contact & Investigator
Armand Mekontso
STUDY CHAIR
Assistance Publique - Hôpitaux de Paris
Frequently Asked Questions
Who can join the NCT03976180 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, studying Sickle Cell Disease. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
Is NCT03976180 currently recruiting?
Yes, NCT03976180 is actively recruiting participants. Contact the research team at armand.dessap@aphp.fr for enrollment information.
Where is the NCT03976180 trial being conducted?
This trial is being conducted at Créteil, France.
Who is sponsoring the NCT03976180 clinical trial?
NCT03976180 is sponsored by Assistance Publique - Hôpitaux de Paris. The principal investigator is Armand Mekontso at Assistance Publique - Hôpitaux de Paris. The trial plans to enroll 350 participants.
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