Protocol and design of the REPOSE study: a double-blinded, randomised, placebo-controlled trial to evaluate the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older patients undergoing non-cardiac surgery
Introduction Postoperative delirium occurs in up to 40% of older surgical patients and has been associated with prolonged hospital stays, long-term cognitive impairment and increased 1-year postoperative mortality. Postoperative sleep disturbances may increase the risk of delirium, but studies inves...
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BMJ Publishing Group
2025-03-01
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| author | Karthik Raghunathan John Michael Fallon Mona Hashemaghaie Christy E Peterson Dieplinh Tran Sophie R Wu Jonathan M Valdes Nicole M Pedicini Melissa E Adams Marjorie Soltis Wissam Mansour Mary Cooter Wright Miriam M Treggiari Cina Sasannejad Michael J Devinney |
| author_facet | Karthik Raghunathan John Michael Fallon Mona Hashemaghaie Christy E Peterson Dieplinh Tran Sophie R Wu Jonathan M Valdes Nicole M Pedicini Melissa E Adams Marjorie Soltis Wissam Mansour Mary Cooter Wright Miriam M Treggiari Cina Sasannejad Michael J Devinney |
| author_sort | Karthik Raghunathan |
| collection | DOAJ |
| description | Introduction Postoperative delirium occurs in up to 40% of older surgical patients and has been associated with prolonged hospital stays, long-term cognitive impairment and increased 1-year postoperative mortality. Postoperative sleep disturbances may increase the risk of delirium, but studies investigating pharmacotherapies to improve postoperative sleep to prevent delirium remain limited. Suvorexant is a selective antagonist of orexin 1 and 2 receptors and is approved for insomnia pharmacotherapy by the Food and Drug Administration. It has the potential to improve postoperative sleep and reduce postoperative delirium rates, but randomised controlled trials (RCTs) are needed to determine the efficacy of postoperative suvorexant administration. The REPOSE study (reducing delirium by enhancing postoperative sleep with suvorexant) is a single-centre, randomised, double-blinded RCT that aims to evaluate the efficacy of suvorexant in increasing total sleep time (TST) and decreasing delirium severity in older patients undergoing non-cardiac surgery.Methods and analysis REPOSE will enroll 130 patients (aged ≥65 years) undergoing non-cardiac surgery with a planned postoperative inpatient stay. Participants will be randomised to receive 20 mg oral suvorexant or placebo nightly on postoperative nights 0, 1 and 2. The primary endpoint is TST on the first postoperative night, as measured using an electroencephalography headband. The secondary endpoint is peak postoperative delirium severity as measured by the 3-minute diagnostic interview for the confusion assessment method severity scores. Primary endpoint data will be analysed with a two-sample t-test using an intent-to-treat approach to compare TST on the first night that a patient received a study drug dose. Secondary and exploratory endpoint data will be analysed using two-sample t-tests between groups.Ethics and dissemination Ethical approval was obtained from the Duke Institutional Review Board (protocol #00111869). Results of the REPOSE study will be published in a peer-reviewed journal and presented at academic conferences. Trial data will be deposited in ClinicalTrials.gov.Trial registration number NCT05733286. |
| format | Article |
| id | doaj-art-6600709daec84e0faa189bde43b1064f |
| institution | OA Journals |
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| language | English |
| publishDate | 2025-03-01 |
| publisher | BMJ Publishing Group |
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| spelling | doaj-art-6600709daec84e0faa189bde43b1064f2025-08-20T02:10:32ZengBMJ Publishing GroupBMJ Open2044-60552025-03-0115310.1136/bmjopen-2024-091099Protocol and design of the REPOSE study: a double-blinded, randomised, placebo-controlled trial to evaluate the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older patients undergoing non-cardiac surgeryKarthik Raghunathan0John Michael Fallon1Mona Hashemaghaie2Christy E Peterson3Dieplinh Tran4Sophie R Wu5Jonathan M Valdes6Nicole M Pedicini7Melissa E Adams8Marjorie Soltis9Wissam Mansour10Mary Cooter Wright11Miriam M Treggiari12Cina Sasannejad13Michael J Devinney142 Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA1 Duke University, Trinity College of Arts and Sciences, Durham, North Carolina, USA2 Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA2 Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA3 Louisiana State University School of Medicine, New Orleans, Louisiana, USA4 Duke University Pratt School of Engineering, Durham, North Carolina, USA1 Duke University, Trinity College of Arts and Sciences, Durham, North Carolina, USA1 Duke University, Trinity College of Arts and Sciences, Durham, North Carolina, USA2 Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA5 Department of Neurology, Duke University School of Medicine, Durham, North Carolina, USA6 Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA2 Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA2 Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA5 Department of Neurology, Duke University School of Medicine, Durham, North Carolina, USA2 Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USAIntroduction Postoperative delirium occurs in up to 40% of older surgical patients and has been associated with prolonged hospital stays, long-term cognitive impairment and increased 1-year postoperative mortality. Postoperative sleep disturbances may increase the risk of delirium, but studies investigating pharmacotherapies to improve postoperative sleep to prevent delirium remain limited. Suvorexant is a selective antagonist of orexin 1 and 2 receptors and is approved for insomnia pharmacotherapy by the Food and Drug Administration. It has the potential to improve postoperative sleep and reduce postoperative delirium rates, but randomised controlled trials (RCTs) are needed to determine the efficacy of postoperative suvorexant administration. The REPOSE study (reducing delirium by enhancing postoperative sleep with suvorexant) is a single-centre, randomised, double-blinded RCT that aims to evaluate the efficacy of suvorexant in increasing total sleep time (TST) and decreasing delirium severity in older patients undergoing non-cardiac surgery.Methods and analysis REPOSE will enroll 130 patients (aged ≥65 years) undergoing non-cardiac surgery with a planned postoperative inpatient stay. Participants will be randomised to receive 20 mg oral suvorexant or placebo nightly on postoperative nights 0, 1 and 2. The primary endpoint is TST on the first postoperative night, as measured using an electroencephalography headband. The secondary endpoint is peak postoperative delirium severity as measured by the 3-minute diagnostic interview for the confusion assessment method severity scores. Primary endpoint data will be analysed with a two-sample t-test using an intent-to-treat approach to compare TST on the first night that a patient received a study drug dose. Secondary and exploratory endpoint data will be analysed using two-sample t-tests between groups.Ethics and dissemination Ethical approval was obtained from the Duke Institutional Review Board (protocol #00111869). Results of the REPOSE study will be published in a peer-reviewed journal and presented at academic conferences. Trial data will be deposited in ClinicalTrials.gov.Trial registration number NCT05733286.https://bmjopen.bmj.com/content/15/3/e091099.full |
| spellingShingle | Karthik Raghunathan John Michael Fallon Mona Hashemaghaie Christy E Peterson Dieplinh Tran Sophie R Wu Jonathan M Valdes Nicole M Pedicini Melissa E Adams Marjorie Soltis Wissam Mansour Mary Cooter Wright Miriam M Treggiari Cina Sasannejad Michael J Devinney Protocol and design of the REPOSE study: a double-blinded, randomised, placebo-controlled trial to evaluate the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older patients undergoing non-cardiac surgery BMJ Open |
| title | Protocol and design of the REPOSE study: a double-blinded, randomised, placebo-controlled trial to evaluate the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older patients undergoing non-cardiac surgery |
| title_full | Protocol and design of the REPOSE study: a double-blinded, randomised, placebo-controlled trial to evaluate the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older patients undergoing non-cardiac surgery |
| title_fullStr | Protocol and design of the REPOSE study: a double-blinded, randomised, placebo-controlled trial to evaluate the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older patients undergoing non-cardiac surgery |
| title_full_unstemmed | Protocol and design of the REPOSE study: a double-blinded, randomised, placebo-controlled trial to evaluate the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older patients undergoing non-cardiac surgery |
| title_short | Protocol and design of the REPOSE study: a double-blinded, randomised, placebo-controlled trial to evaluate the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older patients undergoing non-cardiac surgery |
| title_sort | protocol and design of the repose study a double blinded randomised placebo controlled trial to evaluate the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older patients undergoing non cardiac surgery |
| url | https://bmjopen.bmj.com/content/15/3/e091099.full |
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