High-flow oxygen to treat sickle cell pain crises

A Multicentre, Prospective, Randomized, Multi-arm, Multi-stage Clinical Trial of High-flow Oxygen for Vaso-occlusive Pain Crisis in Adult Patients With Sickle Cell Disease;

This will test whether high-flow nasal oxygen helps adults with sickle cell disease during vaso-occlusive pain crises and lowers the risk of developing acute chest syndrome.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 350 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (other)
• Locations: 1 site (Créteil)
• Trial ID: NCT03976180 on ClinicalTrials.gov

What this trial studies

Adults with major sickle cell genotypes who present with a vaso-occlusive pain crisis and are at intermediate-to-high risk for acute chest syndrome are enrolled. Participants are assigned to standard low-flow nasal oxygen or to high-flow nasal oxygen delivered at one of three FiO2 settings (low 21–30%, intermediate 50%, or high 100%) while receiving usual supportive care. The approach aims to reduce hypoxic stimulus that promotes HbS polymerization and thereby interrupt vaso-occlusion and prevent secondary ACS. Patients with a primary acute chest syndrome at the time of enrollment are excluded.

Who should consider this trial

Good fit: Adults (≥18) with major sickle cell genotypes (SS, SC, Sβ0, Sβ+) experiencing a VOC and classified as intermediate-to-high risk for secondary ACS by PRESEV criteria are the intended participants.

Not a fit: Patients who already have primary acute chest syndrome at enrollment, children, or people judged at low risk for ACS are unlikely to benefit from this intervention in the trial context.

Why it matters

Potential benefit: If successful, using high-flow oxygen could reduce progression from vaso-occlusive crisis to acute chest syndrome and lower related pain, complications, and hospital morbidity.

How similar studies have performed: High-flow nasal oxygen has shown benefit in other acute respiratory settings, but randomized or large studies specifically testing HFNO in sickle-cell vaso-occlusive crises are limited and prior data are small or inconclusive.

Eligibility criteria

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; in case of long-term treatment by hydroxyurea, only one of the above mentioned criteria will be needed, given its effects on hemoglobin, leucocyte and reticulocytes counts;
* 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 randomization 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 with need of parenteral opioids 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;
* Known cerebral vasculopathy or past medical history of stroke, due to Moya Moya or persisting visible macrovessel stenosis/occlusion;
* Known ischemic heart disease or typical chest angina;
* Patient who is currently enrolled in other investigational drug study;
* Known legal incapacity,
* Prisoners or subjects who are involuntarily incarcerated
* Anatomical factors precluding placement of a nasal cannula

Where this trial is running

Créteil

• Henri Mondor — Créteil, France (RECRUITING)

Study contacts

• Study coordinator: Armand Mekontso, MD, PhD

Conditions: Sickle Cell Disease, vaso-occlusive pain crisis, HFNO, ACS