Continuous Positive Airway Pressure for Hypoxemic Acute Chest Syndrome in Patients With Sickle Cell Disease
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 140
- 主要终点
- Time to résolution of acute chest syndrome (ACS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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 <
- •Known pregnancy, breast feeding, women with childbearing potential will be tested for pregnancy and excluded if pregnant,
研究组 & 干预措施
O2+CPAP group
ACS episodes assigned to this group will receive supplemental O2 in addition to periods of CPAP.
干预措施: O2+CPAP group (Other)
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.
结局指标
主要结局
Time to résolution of acute chest syndrome (ACS)
时间窗: Up to randomization
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).
次要结局
- 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)
- 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)
- Length of ICU stay(up to hospital discharge or day-28 after randomisation (whichever occurs first), and at 3 months after randomisation.)
- 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.)
- Quality of life questionary(At inclusion, Day-28, and 3 months)