Protocol for a multicentric, double-blind, randomised controlled trial of hyperbaric oxygen therapy (HBOT) versus sham for treating vaso-occlusive crisis (VOC) in sickle cell disease (SCD) in patients aged 8 years or older (HBOT-SCD study)
Introduction Sickle cell disease (SCD) is one of the most common genetic diseases in the world, annually affecting approximately 310 000 births and causing >100 000 deaths. Vaso-occlusive crisis (VOC) is the most frequent complication of SCD, leading to bone pain, thoracic pain (acute chest s...
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2024-11-01
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| author | Thomas Agoritsas Alain Gervaix Sylvain Boet Pierre Cougoul Cyril Sahyoun Jerôme Stirnemann Benoît Desgraz Olivier Grosgurin Jean-Luc Reny Jacques Serratrice Yves Chalandon Marc Ansari Pierre Louge Tamara Mann Combescure Christophe Kaveh Samii Rodrigue Pignel Giovanna Cannas Laurent Cimasoni Thierry Joffre Claude Lae Marie-Anne Magnan Etienne Menager Annie Momo Bona Marc-Alain Panchard Michel Pellegrini Beatrice Riu |
| author_facet | Thomas Agoritsas Alain Gervaix Sylvain Boet Pierre Cougoul Cyril Sahyoun Jerôme Stirnemann Benoît Desgraz Olivier Grosgurin Jean-Luc Reny Jacques Serratrice Yves Chalandon Marc Ansari Pierre Louge Tamara Mann Combescure Christophe Kaveh Samii Rodrigue Pignel Giovanna Cannas Laurent Cimasoni Thierry Joffre Claude Lae Marie-Anne Magnan Etienne Menager Annie Momo Bona Marc-Alain Panchard Michel Pellegrini Beatrice Riu |
| author_sort | Thomas Agoritsas |
| collection | DOAJ |
| description | Introduction Sickle cell disease (SCD) is one of the most common genetic diseases in the world, annually affecting approximately 310 000 births and causing >100 000 deaths. Vaso-occlusive crisis (VOC) is the most frequent complication of SCD, leading to bone pain, thoracic pain (acute chest syndrome) and/or abdominal spasms. It is the main cause of mortality in patients with SCD, reducing life expectancy. Hyperbaric oxygen therapy (HBOT) is a safe and well-established method of increasing tissue oxygen delivery immediately by up to 10-fold to 20-fold. In the context of VOC, HBOT has the potential to limit sickling. A previous pilot study of nine patients showed the safety and potential benefits of HBOT on VOC-induced pain. Our study aimed to assess the clinical safety and effectiveness of HBOT for treating VOC, its biological mechanisms of actions and its cost-effectiveness.Methods and analysis This is a multicentric, triple-blinded, randomised controlled trial. Patients aged 8 years or above with a diagnosed major form of SCD, presenting at one of the participating centres’ emergency departments (EDs) with a VOC requiring level 3 analgesia (according to WHO definition), will be eligible. Exclusion criteria are pregnancy, mechanical ventilation, previous history of stroke or prior transcranial Doppler ultrasound anomaly, contraindication to HBOT and the need for above 2 L/min of oxygen. All patients will receive the usual care for VOCs, including hydration, analgesics, normobaric oxygen therapy and when medically indicated, antibiotic therapy and/or transfusions. Within 24 hours of their arrival in the ED (or longer in specific cases), and after obtaining informed consent, patients will be randomised into the HBOT intervention group (2.0 atmosphere absolute (ATA), 90 min, FIO2=1) or the sham group (1.3 ATA, 90 min, FIO2=0.21). After their first HBOT session, patients will return to their acute-care ward. Patients in both arms will undergo a second and third session within 24–36 hours of the first, unless their Visual Analogue Scale (VAS)-pain is ≤2 without use of level 3 analgesics. The difference in the pain-VAS before and after HBOT and other outcomes will be compared between the intervention and sham groups. Our composite primary outcome will be (1) the change in global VAS-pain 6 hours after initiation of HBOT; (2) the number of patients with a VAS-pain score >4 and/or a morphine dosage >1 mg/hour intravenous after the HBOT/sham session. Other outcomes to be reported are morphine usage, length of stay, biological parameters, satisfaction, complications and cost.Ethics and dissemination Ethical approval CER Geneva 2019-01707 (last submission V.5.1, 06.15.2023). The results of the studies will be disseminated by several media, including publications in peer-reviewed international medical journals, and presentations at national and/or international conferences.Trial registration number NCT04978116. |
| format | Article |
| id | doaj-art-7038d538426749d19b8ab3c825c25e77 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-7038d538426749d19b8ab3c825c25e772024-12-14T23:35:09ZengBMJ Publishing GroupBMJ Open2044-60552024-11-01141110.1136/bmjopen-2024-084825Protocol for a multicentric, double-blind, randomised controlled trial of hyperbaric oxygen therapy (HBOT) versus sham for treating vaso-occlusive crisis (VOC) in sickle cell disease (SCD) in patients aged 8 years or older (HBOT-SCD study)Thomas Agoritsas0Alain Gervaix1Sylvain Boet2Pierre Cougoul3Cyril Sahyoun4Jerôme Stirnemann5Benoît Desgraz6Olivier Grosgurin7Jean-Luc Reny8Jacques Serratrice9Yves Chalandon10Marc Ansari11Pierre Louge12Tamara Mann13Combescure Christophe14Kaveh Samii15Rodrigue Pignel16Giovanna Cannas17Laurent Cimasoni18Thierry Joffre19Claude Lae20Marie-Anne Magnan21Etienne Menager22Annie Momo Bona23Marc-Alain Panchard24Michel Pellegrini25Beatrice Riu26Department of Medicine, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Women-Children-Teenagers, Geneva University Hospitalse, Geneva, SwitzerlandSubaquatic and Hyperbaric Medicine Unit, Emergency Service, Acute Medicine Department, Geneva University Hospitals, Geneva, SwitzerlandSickle-cell Reference Center, Institut Universitaire du Cancer de Toulouse Oncopole CHU Toulouse, Toulouse, Occitanie, FranceDepartment of Women-Children-Teenagers, Geneva University Hospitals Children`s Hospital, Geneva, SwitzerlandDepartment of Medicine, Geneva University Hospitals, Geneva, SwitzerlandSubaquatic and Hyperbaric Medicine Unit, Emergency Service, Acute Medicine Department, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Medicine, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Medicine, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Medicine, Geneva University Hospitals, Geneva, SwitzerlandHematology Department, Geneva University Hospitals, Geneva, SwitzerlandCANSEARCH Research Platform in Paediatric Oncology and Haematology of the University of Geneva, University of Geneva, Geneva, SwitzerlandSubaquatic and Hyperbaric Medicine Unit, Emergency Service, Acute Medicine Department, Geneva University Hospitals, Geneva, SwitzerlandDepartment of Medicine, Geneva University Hospitals, Geneva, SwitzerlandDiagnostic of Health and Community Medicine, Geneva University Hospitals, Geneva, SwitzerlandDivision of Haematology, Geneva University Hospitals, Geneva, SwitzerlandSubaquatic and Hyperbaric Medicine Unit, Emergency Service, Acute Medicine Department, Geneva University Hospitals, Geneva, SwitzerlandSickle-Cell Disease Reference Center, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes, FranceDivision of Paediatric Oncology and Haematology, Geneva University Hospitals, Geneva, SwitzerlandHyperbaric Center, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes, FranceSubaquatic and Hyperbaric Medicine Unit, Emergency Service, Acute Medicine Department, Geneva University Hospitals, Geneva, SwitzerlandSubaquatic and Hyperbaric Medicine Unit, Emergency Service, Acute Medicine Department, Geneva University Hospitals, Geneva, SwitzerlandSubaquatic and Hyperbaric Medicine Unit, Emergency Service, Acute Medicine Department, Geneva University Hospitals, Geneva, SwitzerlandEmergency Department, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, Occitanie, FranceSubaquatic and Hyperbaric Medicine Unit, Emergency Service, Acute Medicine Department, Geneva University Hospitals, Geneva, SwitzerlandSubaquatic and Hyperbaric Medicine Unit, Emergency Service, Acute Medicine Department, Geneva University Hospitals, Geneva, SwitzerlandHyperbaric Center, Institut Universitaire du Cancer de Toulouse Oncopole CHU Toulouse, Toulouse, Occitanie, FranceIntroduction Sickle cell disease (SCD) is one of the most common genetic diseases in the world, annually affecting approximately 310 000 births and causing >100 000 deaths. Vaso-occlusive crisis (VOC) is the most frequent complication of SCD, leading to bone pain, thoracic pain (acute chest syndrome) and/or abdominal spasms. It is the main cause of mortality in patients with SCD, reducing life expectancy. Hyperbaric oxygen therapy (HBOT) is a safe and well-established method of increasing tissue oxygen delivery immediately by up to 10-fold to 20-fold. In the context of VOC, HBOT has the potential to limit sickling. A previous pilot study of nine patients showed the safety and potential benefits of HBOT on VOC-induced pain. Our study aimed to assess the clinical safety and effectiveness of HBOT for treating VOC, its biological mechanisms of actions and its cost-effectiveness.Methods and analysis This is a multicentric, triple-blinded, randomised controlled trial. Patients aged 8 years or above with a diagnosed major form of SCD, presenting at one of the participating centres’ emergency departments (EDs) with a VOC requiring level 3 analgesia (according to WHO definition), will be eligible. Exclusion criteria are pregnancy, mechanical ventilation, previous history of stroke or prior transcranial Doppler ultrasound anomaly, contraindication to HBOT and the need for above 2 L/min of oxygen. All patients will receive the usual care for VOCs, including hydration, analgesics, normobaric oxygen therapy and when medically indicated, antibiotic therapy and/or transfusions. Within 24 hours of their arrival in the ED (or longer in specific cases), and after obtaining informed consent, patients will be randomised into the HBOT intervention group (2.0 atmosphere absolute (ATA), 90 min, FIO2=1) or the sham group (1.3 ATA, 90 min, FIO2=0.21). After their first HBOT session, patients will return to their acute-care ward. Patients in both arms will undergo a second and third session within 24–36 hours of the first, unless their Visual Analogue Scale (VAS)-pain is ≤2 without use of level 3 analgesics. The difference in the pain-VAS before and after HBOT and other outcomes will be compared between the intervention and sham groups. Our composite primary outcome will be (1) the change in global VAS-pain 6 hours after initiation of HBOT; (2) the number of patients with a VAS-pain score >4 and/or a morphine dosage >1 mg/hour intravenous after the HBOT/sham session. Other outcomes to be reported are morphine usage, length of stay, biological parameters, satisfaction, complications and cost.Ethics and dissemination Ethical approval CER Geneva 2019-01707 (last submission V.5.1, 06.15.2023). The results of the studies will be disseminated by several media, including publications in peer-reviewed international medical journals, and presentations at national and/or international conferences.Trial registration number NCT04978116.https://bmjopen.bmj.com/content/14/11/e084825.full |
| spellingShingle | Thomas Agoritsas Alain Gervaix Sylvain Boet Pierre Cougoul Cyril Sahyoun Jerôme Stirnemann Benoît Desgraz Olivier Grosgurin Jean-Luc Reny Jacques Serratrice Yves Chalandon Marc Ansari Pierre Louge Tamara Mann Combescure Christophe Kaveh Samii Rodrigue Pignel Giovanna Cannas Laurent Cimasoni Thierry Joffre Claude Lae Marie-Anne Magnan Etienne Menager Annie Momo Bona Marc-Alain Panchard Michel Pellegrini Beatrice Riu Protocol for a multicentric, double-blind, randomised controlled trial of hyperbaric oxygen therapy (HBOT) versus sham for treating vaso-occlusive crisis (VOC) in sickle cell disease (SCD) in patients aged 8 years or older (HBOT-SCD study) BMJ Open |
| title | Protocol for a multicentric, double-blind, randomised controlled trial of hyperbaric oxygen therapy (HBOT) versus sham for treating vaso-occlusive crisis (VOC) in sickle cell disease (SCD) in patients aged 8 years or older (HBOT-SCD study) |
| title_full | Protocol for a multicentric, double-blind, randomised controlled trial of hyperbaric oxygen therapy (HBOT) versus sham for treating vaso-occlusive crisis (VOC) in sickle cell disease (SCD) in patients aged 8 years or older (HBOT-SCD study) |
| title_fullStr | Protocol for a multicentric, double-blind, randomised controlled trial of hyperbaric oxygen therapy (HBOT) versus sham for treating vaso-occlusive crisis (VOC) in sickle cell disease (SCD) in patients aged 8 years or older (HBOT-SCD study) |
| title_full_unstemmed | Protocol for a multicentric, double-blind, randomised controlled trial of hyperbaric oxygen therapy (HBOT) versus sham for treating vaso-occlusive crisis (VOC) in sickle cell disease (SCD) in patients aged 8 years or older (HBOT-SCD study) |
| title_short | Protocol for a multicentric, double-blind, randomised controlled trial of hyperbaric oxygen therapy (HBOT) versus sham for treating vaso-occlusive crisis (VOC) in sickle cell disease (SCD) in patients aged 8 years or older (HBOT-SCD study) |
| title_sort | protocol for a multicentric double blind randomised controlled trial of hyperbaric oxygen therapy hbot versus sham for treating vaso occlusive crisis voc in sickle cell disease scd in patients aged 8 years or older hbot scd study |
| url | https://bmjopen.bmj.com/content/14/11/e084825.full |
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