Statistical analysis plan for a cluster-randomised trial assessing the effectiveness of implementation of a bedside evidence-based checklist for clinical management of brain-dead potential organ donors in intensive care units: DONORS (Donation Network to Optimise Organ Recovery Study).
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ABSTRACT: Background
The quality of clinical care of brain-dead potential organ donors may help reduce donor losses caused by irreversible or unreversed cardiac arrest and increase the number of organs donated. We sought to determine whether an evidence-based, goal-directed checklist for donor management in intensive care units (ICUs) can reduce donor losses to cardiac arrest.Methods/design
The DONORS study is a multicentre, cluster-randomised controlled trial with a 1:1 allocation ratio designed to compare an intervention group (goal-directed checklist for brain-dead potential organ donor management) with a control group (standard ICU care). The primary outcome is loss of potential donors due to cardiac arrest. Secondary outcomes are the number of actual organ donors and the number of solid organs recovered per actual donor. Exploratory outcomes include the achievement of relevant clinical goals during the management of brain-dead potential organ donors. The present statistical analysis plan (SAP) describes all primary statistical procedures that will be used to evaluate the results and perform exploratory and sensitivity analyses of the trial.Discussion
The SAP of the DONORS study aims to describe its analytic procedures, enhancing the transparency of the study. At the moment of SAP subsmission, 63 institutions have been randomised and were enrolling study participants. Thus, the analyses reported herein have been defined before the end of the study recruitment and database locking.Trial registration
ClinicalTrials.gov, NCT03179020. Registered on 7 June 2017.
SUBMITTER: Giordani NE
PROVIDER: S-EPMC7298918 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:INTRODUCTION:There is an increasing demand for multi-organ donors for organ transplantation programmes. This study protocol describes the Donation Network to Optimise Organ Recovery Study, a planned cluster randomised controlled trial that aims to evaluate the effectiveness of the implementation of an evidence-based, goal-directed checklist for brain-dead potential organ donor management in intensive care units (ICUs) in reducing the loss of potential donors due to cardiac arrest. METHODS AND ANALYSIS:The study will include ICUs of at least 60 Brazilian sites with an average of ≥10 annual notifications of valid potential organ donors. Hospitals will be randomly assigned (with a 1:1 allocation ratio) to the intervention group, which will involve the implementation of an evidence-based, goal-directed checklist for potential organ donor maintenance, or the control group, which will maintain the usual care practices of the ICU. Team members from all participating ICUs will receive training on how to conduct family interviews for organ donation. The primary outcome will be loss of potential donors due to cardiac arrest. Secondary outcomes will include the number of actual organ donors and the number of organs recovered per actual donor. ETHICS AND DISSEMINATION:The institutional review board (IRB) of the coordinating centre and of each participating site individually approved the study. We requested a waiver of informed consent for the IRB of each site. Study results will be disseminated to the general medical community through publications in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER:NCT03179020; Pre-results.
| S-EPMC6597655 | biostudies-literature
Project description:ImportanceThe effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear.ObjectiveTo evaluate the effectiveness of an evidence-based, goal-directed checklist in the clinical management of brain-dead potential donors in the intensive care unit (ICU).Design, setting, and participantsThe Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020.InterventionsHospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care.Main outcomes and measuresThe primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group.ResultsAmong the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 [57.1%]), followed by trauma (485 [31.6%]). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 [48.4%] brain-dead potential donors) and 32 (50.8%) to the control group (792 [51.6%] brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio [RR], 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006).Conclusions and relevanceThis cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist.Trial registrationClinicalTrials.gov Identifier: NCT03179020.
| S-EPMC10722341 | biostudies-literature
Project description:ObjectivesIn the United Kingdom, three people die every day awaiting an organ transplant. To address this, Scotland and England plan to follow Wales and introduce opt-out donor consent. However, emotional barriers, myths, and misconceptions may deter potential registrants. Our objectives were to estimate the number of people who plan to opt-out of the donor register and to test whether emotional barriers (e.g., medical mistrust) differentiated participants within this group. Finally, in an experimental manipulation, we tested whether intention to donate decreased by making emotional barriers more salient and increased following a widely used myth-busting intervention.DesignMixed between-within design.MethodsUK residents (n = 1,202) were asked whether they would choose opt-in, deemed consent, or opt-out/not sure if legislation changes to opt-out. Participants also completed measures of donor intentions at baseline, following a 12-item emotional barriers questionnaire and again, following a 9-item myth-busting intervention.ResultsFindings indicate that 66.1% of participants selected to opt-in to the donor register, 24.3% selected deemed consent, and 9.4% selected opt-out/not sure. Emotional barriers, notably fears surrounding bodily integrity, were significantly elevated in participants who selected opt-out/not sure. Increasing the salience of emotional barriers reduced donor intentions in the opt-out/not sure group. However, dispelling organ donation myths did not increase intention within this group.ConclusionsIf opt-out legislation is introduced in Scotland and England, approximately 10% of participants plan to opt-out or are not sure. Dispelling organ donation myths with facts may not be the best method of overcoming emotional barriers and increasing donor intentions for those planning to opt-out. Statement of contribution What is already known about this subject? In the United Kingdom, three people die every day waiting for an organ transplant. Although 90% of the UK population support organ donation, only 38% are registered donors. To address this, Scotland and England have recently proposed to introduce an opt-out system of donor consent. To date, limited research has investigated public attitudes and intentions regarding opt-out consent laws in Scotland and England. Emotional barriers (e.g., medical mistrust) are key factors that may deter potential registrants. However, no research has examined these barriers in relation to proposed opt-out consent laws. Myth-busting is widely used around the world as part of campaigns promoting organ donation. The NHS currently use a myth-busting feature on their webpage to dispel harmful myths about organ donation; however, there is limited evidence of the impact this has on intentions to become an organ donor. What does this study add? Approximately 10% of UK participants plan to opt-out or are unsure of their decision, if the law changes to opt-out. Emotional barriers, notably, bodily integrity fears, are significantly elevated in people who plan to opt-out. Increasing the salience of emotional barriers reduced donor intentions for people who plan to opt-out. A myth-busting intervention had no effect on donor intentions for people who plan to opt-out of the donor register.
| S-EPMC6587533 | biostudies-literature
Project description:BackgroundThe LOVIT (Lessening Organ Dysfunction with Vitamin C) trial is a blinded multicenter randomized clinical trial comparing high-dose intravenous vitamin C to placebo in patients admitted to the intensive care unit with proven or suspected infection as the main diagnosis and receiving a vasopressor.ObjectiveWe aim to describe a prespecified statistical analysis plan (SAP) for the LOVIT trial prior to unblinding and locking of the trial database.MethodsThe SAP was designed by the LOVIT principal investigators and statisticians, and approved by the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes, and describes the planned primary, secondary, and subgroup analyses.ResultsThe SAP includes a draft participant flow diagram, tables, and planned figures. The primary outcome is a composite of mortality and persistent organ dysfunction (receipt of mechanical ventilation, vasopressors, or new renal replacement therapy) at 28 days, where day 1 is the day of randomization. All analyses will use a frequentist statistical framework. The analysis of the primary outcome will estimate the risk ratio and 95% CI in a generalized linear mixed model with binomial distribution and log link, with site as a random effect. We will perform a secondary analysis adjusting for prespecified baseline clinical variables. Subgroup analyses will include age, sex, frailty, severity of illness, Sepsis-3 definition of septic shock, baseline ascorbic acid level, and COVID-19 status.ConclusionsWe have developed an SAP for the LOVIT trial and will adhere to it in the analysis phase.International registered report identifier (irrid)DERR1-10.2196/36261.
| S-EPMC9166642 | biostudies-literature
Project description:Despite the success of composite tissue allograft (CTA) such as face and hand transplant at improving recipients' quality of life, organ donors' hesitation needs to be better understood. The aim of the study was to assess Canadian organ donors' willingness to donate their face and hands, and the efficacy of an educational intervention.MethodsCanadians registered for organ donation were invited to complete an online survey about CTA. An interactive vignette was introduced part way through to clarify transplant-related concepts, with repeat of questions post-vignette exposure to assess attitudes pliability.ResultsA total of 942 participants completed the survey. Fifty-two percent of donors were willing to donate their face after passing, whereas 80% were willing to donate their hands. Reasons to refuse CTA donation included the risk of upsetting their family, having someone look like them, and wanting their body to remain intact. Donors' willingness to donate their face (38%, P < 0.001) and hands (79%, P = 0.67) decreased following vignette exposure. Comparative analysis of our interventional vignette with a similar study where donors' donation readiness increased after an educational intervention revealed that our vignette lacked a strong enough emotional component to positively impact donors' attitude to CTA, and may have exposed participants to alternatives to transplant they were not previously aware of.ConclusionsCanadian organ donors surveyed were willing to donate their face and hands following death, a willingness reduced after watching our informative vignette. Further qualitative work is required to better understand the educational needs and areas to address to increase donors' acceptance of CTA.
| S-EPMC8615309 | biostudies-literature
Project description: Not available
| S-EPMC10513101 | biostudies-literature
Project description:Brain dead organ donors are the principal source of transplantable organs. However, it is controversial whether brain death is the same as biological death. Therefore, it is unclear whether organ removal in brain death is consistent with the 'dead donor rule', which states that organ removal must not cause death. Our aim was to evaluate the public's opinion about organ removal if explicitly described as causing the death of a donor in irreversible apneic coma. We conducted a cross-sectional internet survey of the American public (n=1096). Questionnaire domains included opinions about a hypothetical scenario of organ removal described as causing the death of a patient in irreversible coma, and items measuring willingness to donate organs after death. Some 71% of the sample agreed that it should be legal for patients to donate organs in the scenario described and 67% agreed that they would want to donate organs in a similar situation. Of the 85% of the sample who agreed that they were willing to donate organs after death, 76% agreed that they would donate in the scenario of irreversible coma with organ removal causing death. There appears to be public support for organ donation in a scenario explicitly described as violating the dead donor rule. Further, most but not all people who would agree to donate when organ removal is described as occurring after death would also agree to donate when organ removal is described as causing death in irreversible coma.
| S-EPMC4392220 | biostudies-literature
Project description:Background and objectivesComprehensive evaluations are required to safeguard voluntarism and minimize harm to living kidney donors. This process is lengthy, invasive, and emotionally challenging, with up to one fifth of potential donors opting out. We aimed to describe donors' experiences of the evaluation process.Design, setting, participants, & measurementsWe conducted 14 focus groups involving 123 kidney donors who completed donation from three transplant centers (Australia and Canada). Transcripts were analyzed thematically.ResultsWe identified six themes reflecting donors' experiences of evaluation. The themes that related to perseverance included emotional investment (prioritizing the recipient's health, desperation for a normal life, protecting eligibility, shame of disappointing others, and overcoming opposition), undeterred by low risks (medical confidence and protection, worthwhile gamble, inherent invincibility, and normalizing risks), and mental preparation (avoiding regret, resolving decisional ambivalence, and managing expectations of recovery). The challenges included underlying fears for health (processing alarming information, unsettling uncertainty, and preoperative panic), system shortfalls (self-advocacy in driving the process, stressful urgency, inconsistent framing of safety, unnerving bodily scrutiny, questioning risk information, and draining finances); and lifestyle interference (living in limbo, onerous lifestyle disruption, and valuing flexibility).ConclusionsPrevious donors described an emotional investment in donating and determination to protect their eligibility, despite having concerns for their health, financial and lifestyle disruption, and opposition from their family or community. Our findings suggest the need to prepare donors for surgery and recovery, minimize anxiety and lifestyle burdens, ensure that donors feel comfortable expressing their fears and concerns, reduce unnecessary delays, and make explicit the responsibilities of donors in their assessment process.
| S-EPMC5672970 | biostudies-literature
Project description:IntroductionIschaemia/reperfusion injuries (IRIs) are associated with poorer survival of kidney grafts from expanded criteria donors. Preclinical studies have shown that mineralocorticoid receptor antagonists (MRAs) prevent acute and chronic post-ischaemic renal dysfunction by limiting IRI. However, data concerning the safety of MRAs in brain-dead donor patients are scarce. We seek to investigate the tolerance of MRAs on the haemodynamics in this population.Methods and analysisCANREO-PMO is a randomised, controlled, single-centre, double-blind study. Brain-dead organ donors hospitalised in intensive care are randomised 1:1 after consent to receive 200 mg potassium canrenoate or its matching placebo every 6 hours until organ procurement. The primary outcome is a hierarchical composite endpoint that includes: (1) cardiocirculatory arrest, (2) the impossibility of kidney procurement, (3) the average hourly dose of norepinephrine/epinephrine between randomisation and departure to the operating room, and (4) the average hourly volume of crystalloids and/or colloids received. Thirty-six patients will be included. The secondary endpoints evaluated among the graft recipients are the: (1) vital status of the kidney graft recipients and serum creatinine level with estimated glomerular filtration rate (GFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) at 3 months after renal transplantation, (2) percentage of patients dependent on dialysis and/or with an estimated GFR <20 mL/min/1.73 m2 at 3 months, (3) vital status of the kidney graft recipients at 3 months, and (4) vital status of the kidney graft recipients and creatinine levels (in μmol/L), with the estimated GFR according to CKD-EPI (in mL/min/1.73 m2), at 1 year, 3 years and 10 years after transplantation.Ethics and disseminationThis trial has full ethical approval (Comité de Protection des Personnes: CPP Ouest II-ANGERS, France), and the written consent of relatives will be obtained. Results will be reported at conferences, peer-reviewed publications and using social media channels.Trial registration numberNCT04714710.
| S-EPMC10582869 | biostudies-literature
Project description:IntroductionWe describe our technique of ex vivo organ perfusion and procurement in donation after deceased brain death (DBD) donors.Material and methodsThis technique comprises warm dissection of liver, kidneys, and heart, in hemodynamically stable DBD donors and perfusing them ex vivo. The cardiac and abdominal dissection can take place simultaneously. As a precaution, the iliac arteries and the abdominal aorta are dissected and kept ready for rapid cannulation and perfusion, should the donor become unstable at any stage.The liver dissection is in principle similar to living donor hepatectomy, where portal dissection is combined with supra and infrahepatic caval dissection to completely mobilize liver to allow it to be removed and perfused ex vivo. The renal dissection is done after hepatic dissection is complete. The sequence of recovery of organ was modified where kidneys were procured first followed by hepatic and cardiac procurement simultaneously.ResultsTwelve multivisceral (liver and kidneys in all and heart in four) procurements have been performed. The average perfusion fluid volume for liver was 3.4 L. All recipients had uneventful postoperative course.ConclusionOur technique has not affected recipient outcomes and with benefits of less use of preservation solution, shortening bench surgery time, and decreasing the propensity of procurement injuries by avoiding cold-phase dissection.
| S-EPMC7527850 | biostudies-literature