CPAP for Hypoxemic Acute Chest Syndrome in Sickle Cell Disease (SIPAP)

Assistance Publique - Hôpitaux de Paris

Status: Begins enrollment in 1 month

Conditions: Sickle Cell Disease (SCD) Patient Hospitalised for Acute Chest Syndrome (ACS) Requiring Supplemental Oxygen

Treatments: Other: O2+CPAP group

Study type: Interventional

Funder types: Other

Identifiers

NCT07703566

2026-A00423-48 (Other Identifier)

APHP251577

Details and patient eligibility

About

Sickle cell disease (SCD) is a severe hemoglobinopathy, considered the first monogenic disease in the world. Acute chest syndrome (ACS), one of the most frequent and serious complications of SCD, is defined by the association of fever and/or acute respiratory symptoms with a new pulmonary infiltrate on chest imaging. ACS is characterized by lung consolidation, severe pulmonary vascular dysfunction, with potential role for regional alveolar hypoxia. Therefore, improving alveolar oxygenation and limiting lung consolidation are key objectives of the treatment of ACS, in addition to ensuring pain relief and giving blood transfusions and antibiotics. Bilevel non-invasive ventilation failed in improving outcomes during ACS (Fartoukh 2010). These results are in accordance with those reported in other forms of acute lung injury (Frat 2015), with conflicting results. Among other explanations, NIV may favour high tidal volume ventilation leading to patient self-inflicted lung injury (P-SILI) (Carteaux 2016). Continuous positive airway pressure (CPAP) is a simple to use and affordable technique for non-invasive ventilatory support, that theoretically exposes to a lower risk of P-SILI (Carteaux 2021). In patients with acute hypoxemic respiratory failure (AHRF), applying a positive pressure to the airway opening has been shown to mitigate the reduction in functional residual capacity and to improve respiratory mechanics and gas exchange. In a randomized controlled trial (RCT) conducted in patients with AHRF, CPAP achieved early physiologic improvement (Delclaux 2000). Recent results also suggest that CPAP reduces the composite outcome of intubation or death in adults with AHRF due to COVID-19 in a large multicentre study (RECOVERY-R) (Perkins 2022). In addition, CPAP can be safely used at early stages in the wards, with a frugal approach, using virtual valves (Carteaux 2021). In patients with SCD, CPAP has shown benefits when used at night in children with sleep apnea (Marshall 2009), or for the peri-operative management (Leff 2007). CPAP is also used in clinical practice for hypoxemic ACS (Heilbronner 2021), but it has not been formally assessed in this setting.

Enrollment: 140 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• SCD patient of all genotypes (SS, SC, S/β0 and S/β+)
• Age ≥ 18 years old
• Hospitalised for ACS (defined as the association of fever and/or acute respiratory symptoms with a new pulmonary infiltrate on chest imaging)
• Requiring supplemental O2 ≥ 2 L/min for SpO2 ≥ 95%
• Informed consent from the patient
• Affiliated to a social security regime

Exclusion criteria

• Patient having both ACS criteria and need for supplemental O2 ≥ 2 L/min for SpO2 ≥ 95% since more than 48 hours
• Requirement for home supplemental O2 or home CPAP / NIV.
• Signs of worsening respiratory failure mandating intubation (as defined in (Helms et al., 2024))
• Current enrolment in another interventional research concerning a respiratory support during ACS
• Known legal incapacity (patients under guardianship or curatorship)
• Exacerbation of asthma, chronic obstructive pulmonary disease or another known or suspected chronic respiratory disease
• Absolute contraindications to CPAP, including any of the following: patient not cooperating or opposing the technique, pneumothorax not drained, chest wound blowing, uncontrollable vomiting, upper gastrointestinal bleeding, craniofacial trauma, severe upper airway obstruction, traumatic tetraplegia at the initial phase, cardiac arrest, shock (need for vasopressor), or Coma Glasgow scale <12.
• Known pregnancy, breast feeding, women with childbearing potential will be tested for pregnancy and excluded if pregnant,

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

O2+CPAP group

Experimental group

Description:

ACS episodes assigned to this group will receive supplemental O2 in addition to periods of CPAP.

Treatment:

Other: O2+CPAP group

O2 group

No Intervention group

Description:

ACS episodes assigned to the O2 group will receive supplemental O2 delivered through nasal cannula or high flow nasal cannula (for needs ≤6, and \>6L/min, respectively) until endotracheal intubation, death, or fulfilment of O2 delivery cessation criteria (SpO2 ≥95% without supplemental O2). SpO2 will be measured on room air, at least every 12 hours.