High-flow Oxygen for Vaso-occlusive Pain Crisis (OSONE)

Assistance Publique - Hôpitaux de Paris

Status: Unknown

Conditions: Sickle Cell Disease

Treatments: Device: HFNO with intermediate FiO2 (50%); Device: HFNO with high FiO2 (100%); Device: Stadard low-flow oxygen; Device: HFNO with low FiO2 (21%-30%)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03976180

P180303J

Details and patient eligibility

About

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.

Enrollment: 350 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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;
• 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 inclusion 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 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;
• Chronic transfusion program;
• Known cerebral vasculopathy or past medical history of stroke;
• Known ischemic heart disease or typical chest angina;
• Patient who is currently enrolled in other investigational drug study;
• Previous participation in this study.
• Known legal incapacity,
• Prisoners or subjects who are involuntarily incarcerated
• Anatomical factors precluding placement of a nasal cannula

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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350 participants in 4 patient groups

standard low-flow oxygen

Active Comparator group

Description:

In the control group, standard low-flow oxygen will be delivered via nasal prongs (LFNO), up to hospital discharge or secondary ACS onset, in order to achieve normoxia (target pulse oxymetry saturation of 95%). This strategy is in accordance with current recommendations and usual care;

Treatment:

Device: Stadard low-flow oxygen

HFNO with low FiO2 (21%-30%)

Experimental group

Description:

HFNO with low FiO2 (21%-30%) targeting normoxia: to test the effect of improved pulmonary function;

Treatment:

Device: HFNO with low FiO2 (21%-30%)

HFNO with intermediate FiO2 (50%)

Experimental group

Description:

HFNO with intermediate FiO2 (50%): to test the combined effect of improved pulmonary function and moderate hyperoxia; in this group, FiO2 will be set at 50% during the first 24 hours of intervention to target moderate hyperoxia, then reduced to 21-30% during the following 48 hours to target normoxia

Treatment:

Device: HFNO with intermediate FiO2 (50%)

HFNO with high FiO2 (100%)

Experimental group

Description:

HFNO with high FiO2 (100%): to test the combined effect of improved pulmonary function and intense hyperoxia; in this group, FiO2 will be set at 100% during the first 24 hours of intervention to target intense hyperoxia, then reduced to 21-30% during the following 48 hours to target normoxia

Treatment:

Device: HFNO with high FiO2 (100%)