High-flow Oxygen for Vaso-occlusive Pain Crisis

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

350 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-27

Study Completion Date

2025-11-27

Brief Summary

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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.

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Detailed Description

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Conditions

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Sickle Cell Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a comparative randomized controlled superiority open-label multi-arm multi-stage (MAMS) trial. The study will use a multi-arm multi-stage (MAMS) trial design with three stages and four arms (one control arm and three intervention arms).

* "Pilot" stage: a formal safety/feasibility testing. Research arms will only continue to recruitment in the next stage if they have been shown to be both safe and feasible, although patient data from all patients and all stages will be included in the final analyses.
* "Activity" stage: an interim comparison of activity using the rate of VOC resolution without complication at day-5 as primary endpoint. At the end of this stage, an interim analysis will be used in order to select the most promising experimental treatment and compare it to control in the subsequent stage ("pick the winner" strategy).
* "Efficacy" stage: final comparison with secondary ACS at day-14 as the primary endpoint.

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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standard 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;

Group Type ACTIVE_COMPARATOR

Stadard low-flow oxygen

Intervention Type DEVICE

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

HFNO with low FiO2 (21%-30%)

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

Group Type EXPERIMENTAL

HFNO with low FiO2 (21%-30%)

Intervention Type DEVICE

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

HFNO with intermediate FiO2 (50%)

HFNO with intermediate FiO2 (50%): to test the combined effect of improved pulmonary function and moderate hyperoxia; in this group, FiO2 will be set at 50% during the first 24 hours of intervention to target moderate hyperoxia, then reduced to 21-30% during the following 48 hours to target normoxia

Group Type EXPERIMENTAL

HFNO with intermediate FiO2 (50%)

Intervention Type DEVICE

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

HFNO with high FiO2 (100%)

HFNO with high FiO2 (100%): to test the combined effect of improved pulmonary function and intense hyperoxia; in this group, FiO2 will be set at 100% during the first 24 hours of intervention to target intense hyperoxia, then reduced to 21-30% during the following 48 hours to target normoxia

Group Type EXPERIMENTAL

HFNO with high FiO2 (100%)

Intervention Type DEVICE

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

Interventions

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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

Intervention Type DEVICE

HFNO with low FiO2 (21%-30%)

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

Intervention Type 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

Intervention Type 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

Intervention Type DEVICE

Other Intervention Names

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Control group Intervention group Intervention group Intervention group

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No