Strategies to Promote ResiliencY (SPRY): a randomised embedded multifactorial adaptative platform (REMAP) clinical trial protocol to study interventions to improve recovery after surgery in high-risk patients
Introduction As the population ages, there is interest in strategies to promote resiliency, especially for frail patients at risk of its complications. The physiological stress of surgery in high-risk individuals has been proposed both as an important cause of accelerated age-related decline in heal...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-09-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/10/9/e037690.full |
| _version_ | 1819145066529161216 |
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| author | Derek C Angus Jennifer Holder-Murray Katherine Moll Reitz Christopher W Seymour Jennifer Vates Melanie Quintana Kert Viele Michelle Detry Michael Morowitz Alison Morris Barbara Methe Jason Kennedy Brian Zuckerbraun Timothy D Girard Oscar C Marroquin Stephen Esper Anne B Newman Scott Berry Matthew Neal |
| author_facet | Derek C Angus Jennifer Holder-Murray Katherine Moll Reitz Christopher W Seymour Jennifer Vates Melanie Quintana Kert Viele Michelle Detry Michael Morowitz Alison Morris Barbara Methe Jason Kennedy Brian Zuckerbraun Timothy D Girard Oscar C Marroquin Stephen Esper Anne B Newman Scott Berry Matthew Neal |
| author_sort | Derek C Angus |
| collection | DOAJ |
| description | Introduction As the population ages, there is interest in strategies to promote resiliency, especially for frail patients at risk of its complications. The physiological stress of surgery in high-risk individuals has been proposed both as an important cause of accelerated age-related decline in health and as a model testing the effectiveness of strategies to improve resiliency to age-related health decline. We describe a randomised, embedded, multifactorial, adaptative platform (REMAP) trial to investigate multiple perioperative interventions, the first of which is metformin and selected for its anti-inflammatory and anti-ageing properties beyond its traditional blood glucose control features.Methods and analysis Within a multihospital, single healthcare system, the Core Protocol for Strategies to Promote ResiliencY (SPRY) will be embedded within both the electronic health record (EHR) and the healthcare culture generating a continuously self-learning healthcare system. Embedding reduces the administrative burden of a traditional trial while accessing and rapidly analysing routine patient care EHR data. SPRY-Metformin is a placebo-controlled trial and is the first SPRY domain evaluating the effectiveness of three metformin dosages across three preoperative durations within a heterogeneous set of major surgical procedures. The primary outcome is 90-day hospital-free days. Bayesian posterior probabilities guide interim decision-making with predefined rules to determine stopping for futility or superior dosing selection. Using response adaptative randomisation, a maximum of 2500 patients allows 77%–92% power, detecting >15% primary outcome improvement. Secondary outcomes include mortality, readmission and postoperative complications. A subset of patients will be selected for substudies evaluating the microbiome, cognition, postoperative delirium and strength.Ethics and dissemination The Core Protocol of SPRY REMAP and associated SPRY-Metformin Domain-Specific Appendix have been ethically approved by the Institutional Review Board and are publicly registered. Results will be publicly available to healthcare providers, patients and trial participants following achieving predetermined platform conclusions.Trial registration number NCT03861767. |
| first_indexed | 2024-12-22T12:52:07Z |
| format | Article |
| id | doaj.art-b9c524c0611f41caaeb63d568cb8ea1b |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-12-22T12:52:07Z |
| publishDate | 2020-09-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-b9c524c0611f41caaeb63d568cb8ea1b2022-12-21T18:25:12ZengBMJ Publishing GroupBMJ Open2044-60552020-09-0110910.1136/bmjopen-2020-037690Strategies to Promote ResiliencY (SPRY): a randomised embedded multifactorial adaptative platform (REMAP) clinical trial protocol to study interventions to improve recovery after surgery in high-risk patientsDerek C Angus0Jennifer Holder-Murray1Katherine Moll Reitz2Christopher W Seymour3Jennifer Vates4Melanie Quintana5Kert Viele6Michelle Detry7Michael Morowitz8Alison Morris9Barbara Methe10Jason Kennedy11Brian Zuckerbraun12Timothy D Girard13Oscar C Marroquin14Stephen Esper15Anne B Newman16Scott Berry17Matthew Neal18Department of Critical Care Medicine, The CRISMA Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA3 Department of Surgery, Division of Colon and Rectal Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USADepartment of Critical Care Medicine, UPMC, Pittsburgh, Pennsylvania, USADepartment of Critical Care Medicine, UPMC, Pittsburgh, Pennsylvania, USABerry Consultants Statistical Innovation, Austin, Texas, USABerry Consultants Statistical Innovation, Austin, Texas, USABerry Consultants Statistical Innovation, Austin, Texas, USADepartment of Surgery, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USADivision of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USADepartment of Medicine, UPMC, Pittsburgh, Pennsylvania, USADepartment of Critical Care Medicine, UPMC, Pittsburgh, Pennsylvania, USADepartment of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USADepartment of Critical Care Medicine, UPMC, Pittsburgh, Pennsylvania, USAClinical Analytics, UPMC Health System, Pittsburgh, Pennsylvania, USAAnesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USADepartment of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USABerry Consultants Statistical Innovation, Austin, Texas, USADepartment of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USAIntroduction As the population ages, there is interest in strategies to promote resiliency, especially for frail patients at risk of its complications. The physiological stress of surgery in high-risk individuals has been proposed both as an important cause of accelerated age-related decline in health and as a model testing the effectiveness of strategies to improve resiliency to age-related health decline. We describe a randomised, embedded, multifactorial, adaptative platform (REMAP) trial to investigate multiple perioperative interventions, the first of which is metformin and selected for its anti-inflammatory and anti-ageing properties beyond its traditional blood glucose control features.Methods and analysis Within a multihospital, single healthcare system, the Core Protocol for Strategies to Promote ResiliencY (SPRY) will be embedded within both the electronic health record (EHR) and the healthcare culture generating a continuously self-learning healthcare system. Embedding reduces the administrative burden of a traditional trial while accessing and rapidly analysing routine patient care EHR data. SPRY-Metformin is a placebo-controlled trial and is the first SPRY domain evaluating the effectiveness of three metformin dosages across three preoperative durations within a heterogeneous set of major surgical procedures. The primary outcome is 90-day hospital-free days. Bayesian posterior probabilities guide interim decision-making with predefined rules to determine stopping for futility or superior dosing selection. Using response adaptative randomisation, a maximum of 2500 patients allows 77%–92% power, detecting >15% primary outcome improvement. Secondary outcomes include mortality, readmission and postoperative complications. A subset of patients will be selected for substudies evaluating the microbiome, cognition, postoperative delirium and strength.Ethics and dissemination The Core Protocol of SPRY REMAP and associated SPRY-Metformin Domain-Specific Appendix have been ethically approved by the Institutional Review Board and are publicly registered. Results will be publicly available to healthcare providers, patients and trial participants following achieving predetermined platform conclusions.Trial registration number NCT03861767.https://bmjopen.bmj.com/content/10/9/e037690.full |
| spellingShingle | Derek C Angus Jennifer Holder-Murray Katherine Moll Reitz Christopher W Seymour Jennifer Vates Melanie Quintana Kert Viele Michelle Detry Michael Morowitz Alison Morris Barbara Methe Jason Kennedy Brian Zuckerbraun Timothy D Girard Oscar C Marroquin Stephen Esper Anne B Newman Scott Berry Matthew Neal Strategies to Promote ResiliencY (SPRY): a randomised embedded multifactorial adaptative platform (REMAP) clinical trial protocol to study interventions to improve recovery after surgery in high-risk patients BMJ Open |
| title | Strategies to Promote ResiliencY (SPRY): a randomised embedded multifactorial adaptative platform (REMAP) clinical trial protocol to study interventions to improve recovery after surgery in high-risk patients |
| title_full | Strategies to Promote ResiliencY (SPRY): a randomised embedded multifactorial adaptative platform (REMAP) clinical trial protocol to study interventions to improve recovery after surgery in high-risk patients |
| title_fullStr | Strategies to Promote ResiliencY (SPRY): a randomised embedded multifactorial adaptative platform (REMAP) clinical trial protocol to study interventions to improve recovery after surgery in high-risk patients |
| title_full_unstemmed | Strategies to Promote ResiliencY (SPRY): a randomised embedded multifactorial adaptative platform (REMAP) clinical trial protocol to study interventions to improve recovery after surgery in high-risk patients |
| title_short | Strategies to Promote ResiliencY (SPRY): a randomised embedded multifactorial adaptative platform (REMAP) clinical trial protocol to study interventions to improve recovery after surgery in high-risk patients |
| title_sort | strategies to promote resiliency spry a randomised embedded multifactorial adaptative platform remap clinical trial protocol to study interventions to improve recovery after surgery in high risk patients |
| url | https://bmjopen.bmj.com/content/10/9/e037690.full |
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