Hyperbaric-oxygen Therapy (HBOT) Versus Placebo for Treating Vaso-Occlusive Crisis (VOC) in Sickle Cell Disease (SCD) (HBOT-SCD)

University Hospitals (UH)

Status and phase: Enrolling; Phase 3

Conditions: Vaso-occlusive Crisis; Hyperbaric Oxygen Therapy; Sickle Cell Disease

Treatments: Device: HBOT in Hyperbaric chamber; Device: Hyperbaric chamber for placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05289700

2019-01707

Details and patient eligibility

About

This is a randomised, controlled, double-blind, placebo trial of HBOT (intervention) superiority in the treatment of VOC in SCD, to demonstrate the effectiveness of HBOT for the decrease in pain level in the treatment of SCD-VOC.

Full description

Background: Sickle cell disease (SCD) is one of the most common genetic diseases in the world, affecting approximately 310,000 births each year and causing >100,000 deaths. Vaso-occlusive crisis (VOC) is the most frequent complication of SCD, leading to bone pain, thoracic pain and/or abdominal spasms and is the main cause of death in patients with SCD. It is linked to sickling which is often triggered by internal and external environmental conditions such as acidosis, cold, dehydration, hyperthermia, infection and especially hypoxia. Sickling is initially reversible if local oxygenation supply and conditions are improved.

Rationale: The use of hyperbaric oxygen therapy (HBOT) should enable the patient's tissues to receive the extra oxygen necessary by increasing the amount of dissolved O2 in blood which in turn would limit sickling. A pilot study of 9 patients showed the potential positive effects of HBOT on VOC induced pain. International guidelines indicate that SCD-induced VOC is one of the potential indications for HBOT, even though the evidence available is weak.

Aim and objectives: To demonstrate the analgesic effect of HBOT for VOC and to analyse the procedure's safety, impact on the biological markers of SCD-induced VOC, progression of SCD and cost-effectiveness.

Methodology: This study will be a multicentric, double-blind, randomised controlled trial. Any patient presenting at one of the participating centres' Emergency Departments (EDs) with VOC is eligible to be evaluated, included and randomized. Inclusion criteria: Patients aged 8 years or over with a major SCD, having a VOC non-responsive to level 2 analgesics (WHO classification), with or without Acute Chest Syndrome (ACS). Exclusion criteria: Pregnancy, indication for artificial ventilation, proven contraindication for HBO, blood velocity > 200 cm/sec previously measured with transcranial Doppler, previous history of stroke, patient requiring more than 2 l/min of normobaric oxygen in order to achieve an SpO2 (peripheral oxygen saturation) ≥ 92%. Patients with exclusion criteria, although precluded from the randomisation process, will however be eligible to undergo the HBOT intervention and become part of the cohort. Measurements and procedures: In all cases, included patients will receive usual care for VOC, including hydration, analgesics (patient-controlled analgesia with morphine), normobaric oxygen therapy and where medically indicated, antibiotic therapy and/or transfusions. Within 4 to 12 hours of their initial consultation at their hospital's ED, patients who have agreed to participate in the study will be randomised between the HBOT intervention group (2 Atmosphere Absolute pressure [ATA], 95 min, FIO2 = 1) and the placebo group (1.3 ATA, 95 min, FIO2 = 0.21). Patients will undergo a first session in the hyperbaric chamber and then return to their ward. The second (and third) session (for both groups) will systematically take place within 24 h (max. 36 h) of the first session. If the visual analogue scale (VAS) pain score is ≤ 2 without the use of level 3 analgesics at the standard dosage, subsequent sessions will be cancelled. Difference in the visual analogue scale (VAS) pain score before and after HBOT and other outcomes will be compared between the intervention and placebo groups. A superiority of HBOT compared placebo group in VOC should be demonstrated, with decrease of pain, length of stay and cost.

Expected results and their impact: Expected benefits of HBOT are the reduction of: pain experienced, duration of the crisis, number of transfusions required, the number of morphine doses, reduction of length of stay and reduction in the frequency of ACSs and VOCs.

Enrollment: 100 estimated patients

Sex: All

Ages: 8+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients aged 8 or over;
• Diagnosed with a major SCD disorder (SS, SC, Hb O Arab, Sβ0 and Sβ+ -thalassemias);
• Presentation of a Vaso-Occlusive Crisis (VOC), with or without Acute Chest Syndrome,
• Unresponsive to level 2 analgesics (WHO classification)
• Which fulfils the criteria necessary for consultation at an ED;
• Ability to carry out the Valsalva manoeuvre;
• Ability to give informed consent and sign a written informed consent form (consent and signature of legal guardian authorised).

Exclusion criteria

• Pregnancy;
• Indication for artificial ventilation (non-invasive ventilation/oro-tracheal intubation);
• Proven contraindication for HBOT established by a physician responsible for hyperbaric medicine;
• Anomaly in the results of prior transcranial Doppler (TCD) ultrasound (> 200 cm/sec) or a previous history of stroke (but TCD will not be performed for the study);
• Patients requiring more than 2 l/min of normobaric oxygen in order to maintain an SpO2 ≥ 92%.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

100 participants in 2 patient groups, including a placebo group

HBOT intervention group (2 ATA, 95 min, FIO2=1)

Experimental group

Description:

Hyperbaric Oxygen Therapy (HBOT) is the administration of oxygen at a pressure higher than atmospheric pressure (2 ATA). By breathing pure oxygen at twice the atmospheric pressure, its concentration in the blood is multiplied by nearly ten times. This allows a greater oxygen concentration in poorly vascularised areas of the body.

Treatment:

Device: HBOT in Hyperbaric chamber

placebo group (1.3 ATA, 95 min, FIO2=0.21)

Placebo Comparator group

Description:

Hyperbaric chamber is the same chamber used for HBOT, but with a limited hyperpressure (1.3 ATA) and using ambient air (FIO2=0.21), with illusion of treatment in healthy volunteers.

Treatment:

Device: Hyperbaric chamber for placebo