CPAP for Hypoxemic Acute Chest Syndrome in Sickle Cell Disease

NCT07703566 | Not Yet Recruiting

• 2 other identifiers: APHP2515772026-A00423-48
• Study Type: interventional
• Target: 140
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Sickle Cell Disease (SCD); Acute Chest Syndrome (ACS)

Keywords

CPAP; Acute chest syndrome (ACS); Sickle cell disease (SCD); supplemental oxygen

Outcome Measures

Primary Outcomes (1)

• Time to résolution of acute chest syndrome (ACS)

  time to resolution of ACS, defined as the time from randomization to the joint resolution of fever (body temperature \< 38°C), chest pain (visual analog scale, VAS ≤ 3 cm, morphine ≤ 40mg/24h), dyspnea (VAS ≤ 3 cm, respiratory rate \< 25/min, no ventilatory support), and hypoxemia (SpO2 \> 92% on room air) (Mekontso Dessap, Habibi, et al., 2025). If a VAS is unavailable, a verbal rating scale will be used. Resolution of ACS will be assessed every 8 to 12 hours and will be considered achieved if sustained across 2 to 3 consecutive evaluations (i.e., over a 24-hour period).

  Up to randomization

Secondary Outcomes (13)

• Mortality

  up to hospital discharge or day-28 after randomisation (whichever occurs first), and at 3 months after randomisation.

• Length of hospital stay

  up to hospital discharge or day-28 after randomisation (whichever occurs first), and at 3 months after randomisation.

• Length of ICU stay

  up to hospital discharge or day-28 after randomisation (whichever occurs first), and at 3 months after randomisation.

• Need for catecholamine infusion

  From randomisation to discharge or Day-28

• Number of red blood cell units transfused

  From randomisation to discharge or Day-28

Study Arms (2)

O2+CPAP group

EXPERIMENTAL

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

Other: O2+CPAP group

O2 group

NO INTERVENTION

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.

Interventions

O2+CPAP group OTHER

ACS episodes assigned to this group will receive supplemental O2 in addition to periods of CPAP. CPAP will target a positive pressure between 5 and 10 cmH2O. CPAP will be given discontinuously (≥6 hours/day) based on patient tolerance . CPAP sessions will be stopped when the patient achieves the criteria for cessation of supplemental O2. These criteria will be the same as in the O2 group. No sedation will be used for CPAP tolerance.

O2+CPAP group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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,

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Anemia, Sickle Cell; Acute Chest Syndrome

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Armand MEKONTSO-DESSAP, MD, PhD

  Assistance public Hôpitaux de Paris

  STUDY CHAIR

Central Study Contacts

Samia BALOUL

CONTACT

01 49 81 33 85; samia.baloul@aphp.fr

Armand MEKONTSO-DESSAP

CONTACT

armand.dessap@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 14, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share