Informations générales (source: ClinicalTrials.gov)
A Multicentre, Prospective, Randomized, Multi-arm, Multi-stage Clinical Trial of High-flow Oxygen for Vaso-occlusive Pain Crisis in Adult Patients With Sickle Cell Disease;
Interventional
N/A
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
avril 2020
novembre 2025
13 septembre 2025
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CENTRE HOSPITALIER DE ST-DENIS | MEKONTSO DESSAP Armand | 27/12/2025 08:03:39 | Contacter | ||
| CENTRE HOSPITALIER SUD FRANCILIEN | MEKONTSO DESSAP Armand | 27/12/2025 08:03:38 | Contacter | ||
| CHI DE CRETEIL | MEKONTSO DESSAP Armand | 27/12/2025 08:03:39 | Contacter | ||
| AP-HP Assistance publique - Hôpitaux de Paris | 27/12/2025 08:03:41 | Contacter | |||
| AP-HP - Hôpital Avicenne | |||||
| AP-HP - Hôpital Bicêtre | |||||
| AP-HP - Hôpital Europeen Georges Pompidou | |||||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | |||||
| AP-HP - Hôpital Jean Verdier | |||||
| AP-HP - Hôpital Louis Mourier | |||||
| AP-HP - Hôpital Necker-Enfants Malades | |||||
| AP-HP - Hôpital Saint Antoine | |||||
| AP-HP - Hôpital Tenon | |||||
Critères
Tous
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
- 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
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