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

Continuous Positive Airway Pressure for Hypoxemic Acute Chest Syndrome in Patients With Sickle Cell Disease

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Sickle Cell Disease (SCD) Patient Hospitalised for Acute Chest Syndrome (ACS) Requiring Supplemental Oxygen
• Intervention / Treatment: Other: O2+CPAP group

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Samia BALOUL; Phone Number: 01 49 81 33 85; Email: samia.baloul@aphp.fr
• Study Contact Backup: Name: Armand MEKONTSO-DESSAP; Email: armand.dessap@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: O2+CPAP group; ACS episodes assigned to this group will receive supplemental O2 in addition to periods of CPAP.	Other: O2+CPAP group; 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.
No Intervention: O2 group; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	All-cause 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	dobutamine, dopamine, adrenaline or noradrenaline	From randomisation to discharge or Day-28
Number of red blood cell units transfused		From randomisation to discharge or Day-28
Volume of blood exsanguination		From randomisation to discharge or Day-28
Need for invasive ventilation		From randomisation to discharge or Day-28
Number of days free from any respiratory support		From randomisation to discharge or Day-28
Need for antibiotics therapy		From randomisation to discharge or Day-28
Change in arterial blood gases (PaO2/FiO2 ratio), routine laboratory markers (lacticodeshydrogenase), and chest imaging (X-ray or lung ultrasound score)		within 3 days post-randomisation
Readmissions for VOC		up to 3 months
Readmissions for ACS		up to 3 months
Quality of life questionary	European Quality of life five-dimensions five-level questionnaire (EQ-5D-5L)	At inclusion, Day-28, and 3 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Chair: Armand MEKONTSO-DESSAP, MD, PhD, Assistance public Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 8, 2026
• First Submitted That Met QC Criteria: July 8, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: CPAP; Sickle cell disease (SCD); supplemental oxygen; Acute chest syndrome (ACS)
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Acute Chest Syndrome
• Other Study ID Numbers: APHP251577; 2026-A00423-48 (Other Identifier: Ministère chargé de la Santé, France)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No