Study protocol of a randomised, double-blind, placebo-controlled, two-arm parallel-group, multi-centre phase 3 pivotal trial to investigate the efficacy and safety of recombinant human alkaline phosphatase for treatment of patients with sepsis-associated acute kidney injury.

INTRODUCTION: Sepsis, the leading cause of acute kidney injury (AKI), is associated with a high morbidity and mortality. Alkaline phosphatase (ALP) is an endogenous detoxifying enzyme. A recombinant human ALP compound, ilofotase alfa, showed no safety or tolerability concerns in a phase 2 trial. Renal function improvement over 28 days was significantly greater in the ilofotase alfa group. Moreover, a significant relative reduction in 28-day all-cause mortality of >40% was observed. A follow-up trial has been designed to confirm these findings. METHODS AND ANALYSIS: This is a phase 3, global, multi-centre, randomised, double-blind, placebo-controlled, sequential design trial in which patients are randomly assigned to either placebo or 1.6 mg/kg ilofotase alfa. Randomisation is stratified by baseline modified Sequential Organ Failure Assessment (mSOFA) score and trial site. The primary objective is to confirm the survival benefit with ilofotase alfa by demonstrating a reduction in 28-day all-cause mortality in patients with sepsis-associated AKI requiring vasopressors. A maximum of 1400 patients will be enrolled at ∼120 sites in Europe, North America, Japan, Australia and New Zealand. Up to four interim analyses will take place. Based on predefined decision rules, the trial may be stopped early for futility or for effectiveness. In addition, patients with COVID-19 disease and patients with 'moderate to severe' chronic kidney disease are analysed as 2 separate cohorts of 100 patients each. An independent Data Monitoring Committee evaluates safety data at prespecified intervals throughout the trial. ETHICS AND DISSEMINATION: The trial is approved by relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, guidelines of Good Clinical Practice, Code of Federal Regulations and all other applicable regulations. Results of this study will determine the potential of ilofotase alfa to reduce mortality in critically ill patients with sepsis-associated AKI and will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: EudraCT CT Number 2019-0046265-24. US IND Number 117 605 Pre-results. CLINICALTRIALS: gov number: NCT04411472.

Perspectives from designated family caregivers of critically ill adult patients during the COVID-19 pandemic: A qualitative interview study.

BACKGROUND: Family visitation in intensive care units (ICU) has been impacted by the severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic. While studies report on perceptions of families completely restricted from ICUs, little is known about the burden experienced by designated family caregivers allowed to visit their critically ill loved one. This study sought the perspectives of family caregivers of critically ill patients on the impact of one-person designated visitor policies mandated in ICUs during the COVID-19 pandemic. METHODS: Throughout the study period a restricted visitation policy was mandated capturing the first (April 2020) and second (December 2020) waves of the pandemic that allowed one designated family caregiver (i.e., spouses or adult children) per patient to visit the ICU. Designated family caregivers of critically ill patients admitted to ICU September 2020 to November 2020 took part in individual 60-minute, semi-structured interviews at 6-months after discharge from the index ICU admission. Themes from family interviews were summarized with representative quotations. RESULTS: Key themes identified following thematic analysis from six participants included: one visitor rule, patient advocate role, information needs, emotional distress, strategies for coping with challenges, practicing empathy, and appreciation of growth. CONCLUSION: Designated family caregivers of critically ill patients admitted to ICU during the COVID-19 pandemic perceived a complex and highly stressful experience. Support from ICU family liaisons and psychologists may help ameliorate the impact.

Evidence-informed consensus statements to guide COVID-19 patient visitation policies: results from a national stakeholder meeting.

PURPOSE: Hospital policies forbidding or limiting families from visiting relatives on the intensive care unit (ICU) has affected patients, families, healthcare professionals, and patient- and family-centered care (PFCC). We sought to refine evidence-informed consensus statements to guide the creation of ICU visitation policies during the current COVID-19 pandemic and future pandemics and to identify barriers and facilitators to their implementation and sustained uptake in Canadian ICUs. METHODS: We created consensus statements from 36 evidence-informed experiences (i.e., impacts on patients, families, healthcare professionals, and PFCC) and 63 evidence-informed strategies (i.e., ways to improve restricted visitation) identified during a modified Delphi process (described elsewhere). Over two half-day virtual meetings on 7 and 8 April 2021, 45 stakeholders (patients, families, researchers, clinicians, decision-makers) discussed and refined these consensus statements. Through qualitative descriptive content analysis, we evaluated the following points for 99 consensus statements: 1) their importance for improving restricted visitation policies; 2) suggested modifications to make them more applicable; and 3) facilitators and barriers to implementing these statements when creating ICU visitation policies. RESULTS: Through discussion, participants identified three areas for improvement: 1) clarity, 2) accessibility, and 3) feasibility. Stakeholders identified several implementation facilitators (clear, flexible, succinct, and prioritized statements available in multiple modes), barriers (perceived lack of flexibility, lack of partnership between government and hospital, change fatigue), and ways to measure and monitor their use (e.g., family satisfaction, qualitative interviews). CONCLUSIONS: Existing guidance on policies that disallowed or restricted visitation in intensive care units were confusing, hard to operationalize, and often lacked supporting evidence. Prioritized, succinct, and clear consensus statements allowing for local adaptability are necessary to guide the creation of ICU visitation policies and to optimize PFCC.

RéSUMé: OBJECTIF: Les politiques hospitalières interdisant ou limitant les visites des familles à des proches à l'unité de soins intensifs (USI) ont affecté les patients, les familles, les professionnels de la santé et les soins centrés sur le patient et la famille (SCPF). Nous avons cherché à affiner les déclarations de consensus fondées sur des données probantes afin de guider la création de politiques de visite aux soins intensifs pendant la pandémie actuelle de COVID-19 et les pandémies futures, et dans le but d'identifier les obstacles et les critères facilitants à leur mise en œuvre et à leur adoption répandue dans les unités de soins intensifs canadiennes. MéTHODE: Nous avons créé des déclarations de consensus à partir de 36 expériences fondées sur des données probantes (c.-à-d. impacts sur les patients, les familles, les professionnels de la santé et les SCPF) et 63 stratégies fondées sur des données probantes (c.-à-d. moyens d'améliorer les restrictions des visites) identifiées au cours d'un processus Delphi modifié (décrit ailleurs). Au cours de deux réunions virtuelles d'une demi-journée tenues les 7 et 8 avril 2021, 45 intervenants (patients, familles, chercheurs, cliniciens, décideurs) ont discuté et affiné ces déclarations de consensus. Grâce à une analyse descriptive qualitative du contenu, nous avons évalué les points suivants pour 99 déclarations de consensus : 1) leur importance pour l'amélioration des politiques de restriction des visites; 2) les modifications suggérées pour les rendre plus applicables; et 3) les critères facilitants et les obstacles à la mise en œuvre de ces déclarations lors de la création de politiques de visite aux soins intensifs. RéSULTATS: En discutant, les participants ont identifié trois domaines à améliorer : 1) la clarté, 2) l'accessibilité et 3) la faisabilité. Les intervenants ont identifié plusieurs critères facilitants à la mise en œuvre (énoncés clairs, flexibles, succincts et hiérarchisés disponibles dans plusieurs modes), des obstacles (manque perçu de flexibilité, manque de partenariat entre le gouvernement et l'hôpital, fatigue du changement) et des moyens de mesurer et de surveiller leur utilisation (p. ex., satisfaction des familles, entrevues qualitatives). CONCLUSION: Les directives existantes sur les politiques qui interdisaient ou limitaient les visites dans les unités de soins intensifs étaient déroutantes, difficiles à mettre en oeuvre et manquaient souvent de données probantes à l'appui. Des déclarations de consensus hiérarchisées, succinctes et claires permettant une adaptabilité locale sont nécessaires pour guider la création de politiques de visite en soins intensifs et pour optimiser les soins centrés sur le patient et la famille.

A Modified Delphi Process to Prioritize Experiences and Guidance Related to ICU Restricted Visitation Policies During the Coronavirus Disease 2019 Pandemic.

To create evidence-based consensus statements for restricted ICU visitation policies to support critically ill patients, families, and healthcare professionals during current and future pandemics. DESIGN: Three rounds of a remote modified Delphi consensus process. SETTING: Online survey and virtual polling from February 2, 2021, to April 8, 2021. SUBJECTS: Stakeholders (patients, families, clinicians, researchers, allied health professionals, decision-makers) admitted to or working in Canadian ICUs during the coronavirus disease 2019 pandemic. MEASUREMENTS AND MAIN RESULTS: During Round 1, key stakeholders used a 9-point Likert scale to rate experiences (1-not significant, 9-significant impact on patients, families, healthcare professionals, or patient- and family-centered care) and strategies (1-not essential, 9-essential recommendation for inclusion in the development of restricted visitation policies) and used a free-text box to capture experiences/strategies we may have missed. Consensus was achieved if the median score was 7-9 or 1-3. During Round 2, participants used a 9-point Likert scale to re-rate experiences/strategies that did not meet consensus during Round 1 (median score of 4-6) and rate new items identified in Round 1. During Rounds 2 and 3, participants ranked items that reached consensus by order of importance (relative to other related items and experiences) using a weighted ranking system (0-100 points). Participants prioritized 11 experiences (e.g., variability of family's comfort with technology, healthcare professional moral distress) and developed 21 consensus statements (e.g., communicate policy changes to the hospital staff before the public, permit visitors at end-of-life regardless of coronavirus disease 2019 status, creating a clear definition for end-of-life) regarding restricted visitation policies. CONCLUSIONS: We have formulated evidence-informed consensus statements regarding restricted visitation policies informed by diverse stakeholders, which could enhance patient- and family-centered care during a pandemic.

Restricted visitation policies in acute care settings during the COVID-19 pandemic: a scoping review.

BACKGROUND: Restricted visitation policies in acute care settings because of the COVID-19 pandemic have negative consequences. The objective of this scoping review is to identify impacts of restricted visitation policies in acute care settings, and describe perspectives and mitigation approaches among patients, families, and healthcare professionals. METHODS: We searched Medline, Embase, PsycINFO, Healthstar, CINAHL, Cochrane Central Register of Controlled Trials on January 01/2021, unrestricted, for published primary research records reporting any study design. We included secondary (e.g., reviews) and non-research records (e.g., commentaries), and performed manual searches in web-based resources. We excluded records that did not report primary data. Two reviewers independently abstracted data in duplicate. RESULTS: Of 7810 citations, we included 155 records. Sixty-six records (43%) were primary research; 29 (44%) case reports or case series, and 26 (39%) cohort studies; 21 (14%) were literature reviews and 8 (5%) were expert recommendations; 54 (35%) were commentary, editorial, or opinion pieces. Restricted visitation policies impacted coping and daily function (n = 31, 20%) and mental health outcomes (n = 29, 19%) of patients, families, and healthcare professionals. Participants described a need for coping and support (n = 107, 69%), connection and communication (n = 107, 69%), and awareness of state of well-being (n = 101, 65%). Eighty-seven approaches to mitigate impact of restricted visitation were identified, targeting families (n = 61, 70%), patients (n = 51, 59%), and healthcare professionals (n = 40, 46%). CONCLUSIONS: Patients, families, and healthcare professionals were impacted by restricted visitation polices in acute care settings during COVID-19. The consequences of this approach on patients and families are understudied and warrant evaluation of approaches to mitigate their impact. Future pandemic policy development should include the perspectives of patients, families, and healthcare professionals. TRIAL REGISTRATION: The review was registered on PROSPERO (CRD42020221662) and a protocol peer-reviewed prior to data extraction.

Impact of restricted visitation policies in hospitals on patients, family members and healthcare providers during the COVID-19 pandemic: a scoping review protocol.

INTRODUCTION: Flexible visitation policies in hospitals are an important component of care that contributes to reduced stress and increased satisfaction among patients and their family members. Early evidence suggests restricted visitation policies enacted in hospitals during the COVID-19 pandemic are having unintended consequences on patients, family members and healthcare providers. There is a need for a comprehensive summary of the impacts of restricted visitation policies on key stakeholders and approaches to mitigate that impact. METHODS AND ANALYSIS: We will conduct a scoping review as per the Arksey-O'Malley 5-stage scoping review method and the Scoping Review Methods Manual by the Joanna Briggs Institute. We will search relevant electronic databases (eg, CINAHL, MEDLINE, PsycINFO), grey literature and preprint repositories. We will include all study designs including qualitative and quantitative methodologies (excluding protocols) as well as reports, opinions and editorials, to identify the broad impact of restricted hospital visitation policies due to the COVID-19 pandemic on patients, family members or healthcare providers of hospitalised patients, and approaches taken or proposed to mitigate this impact. Two reviewers will calibrate the screening criteria and data abstraction form and will independently screen studies and abstract the data. Narrative synthesis with thematic analysis will be performed. ETHICS AND DISSEMINATION: Ethical approval is not applicable as this review will be conducted on published literature only. This scoping review will identify, describe and categorise impacts of restricted hospital visitation policies due to the COVID-19 pandemic on patients, family members and healthcare providers of hospitalised patients, and approaches that have been taken to mitigate impact. We will provide a comprehensive synthesis by developing a framework of restricted visitation policies and associated impacts. Our results will inform the development of consensus statements on restricted visitation policies to be implemented in future pandemics. PROSPERO REGISTRATION NUMBER: CRD42020221662.