High-flow Oxygen for Vaso-occlusive Pain Crisis

Summary

Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive pain crisis (VOC), which may evolve to acute chest syndrome (ACS), the most common cause of death among adult patients with SCD. Currently, there is no safe and effective treatment to abort VOC or prevent secondary ACS. Management of VOC mostly involve a symptomatic approach including hydration, analgesics, transfusion, and incentive spirometry, which was investigated in a very limited number of patients (\<30).

The polymerisation of HbS is one major feature in the pathogenesis of vaso-occlusion. Among factors determining the rate and extent of HbS polymer formation, the hypoxic stimulus is one of the most potent and readily alterable. Current guidelines recommend oxygen therapy in patients with VOC in order to maintain a target oxygen saturation of 95%. Low-flow nasal oxygen (LFNO) is routinely used to achieve this normoxia approach, particularly in patients at risk of secondary ACS because they may experience acute desaturation. In contrast, various case series suggest a potential beneficial role of intensified oxygen therapy targeting hyperoxia for the management of VOC, particularly with the use of hyperbaric oxygen, but the latter is difficult to implement in routine clinical practice.

A recent high-flow nasal oxygen (HFNO) technology allows the delivery of humidified gas at high fraction of inspired oxygen (FiO2) through nasal cannula. The FiO2 can be adjusted up to 100% (allowing hyperoxia that may reverse sickling) and the flow can be increased up to 60 L/min (which generates positive airway pressure and dead space flushing, that may prevent evolution of VOC towards ACS by alleviating atelectasis and opioid-induced hypercapnia). In patients with acute respiratory failure, HFNO has been shown to improve patient's comfort, oxygenation, and survival as compared to standard oxygen or non-invasive ventilation.

The aim of the present study is to test the efficacy and safety of HFNO for the management of VOC and prevention of secondary ACS. The investigators will use a multi-arm multi-stage (MAMS) design to achieve these goals. HFNO will be delivered through AIRVO 2 (Fisher and Paykel Healthcare, New Zealand), a device that incorporates a turbine allowing its use in hospital wards.

Conditions

• Sickle Cell Disease

Interventions

DEVICE

Stadard low-flow oxygen

In the control group, standard low-flow oxygen will be delivered via nasal prongs (LFNO), up to hospital discharge or secondary ACS onset, in order to achieve normoxia (target pulse oxymetry saturation of 95%). This strategy is in accordance with current recommendations and usual care

DEVICE

HFNO with low FiO2 (21%-30%)

HFNO with low FiO2 (21%-30%) targeting normoxia: to test the effect of improved pulmonary function

DEVICE

HFNO with intermediate FiO2 (50%)

In this group, FiO2 will be set at 50% during the first 24 hours of intervention to target moderate hyperoxia, then reduced to 21-3025% during the following 48 hours to target normoxia

DEVICE

HFNO with high FiO2 (100%)

In this group, FiO2 will be set at 100% during the first 24 hours of intervention to target intense hyperoxia, then reduced to 21-3025% during the following 48 hours to target normoxia

Sponsors & Collaborators

• Fisher and Paykel Healthcare

  collaborator INDUSTRY

• Orkyn'

  collaborator INDUSTRY

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Armand Mekontso · Assistance Publique - Hôpitaux de Paris

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-04-27

Primary Completion

2025-11-27

Completion

2025-11-27

Countries

• France

Study Locations