Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine (HERO-HCQ).

OBJECTIVES: To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCWs). METHODS: In a 1: 1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial at 34 US clinical centers, 1360 HCWs at risk for COVID-19 infection were enrolled between April and November 2020. Participants were randomized to HCQ or matched placebo. The HCQ dosing included a loading dose of HCQ 600 mg twice on day 1, followed by 400 mg daily for 29 days. The primary outcome was a composite of confirmed or suspected COVID-19 clinical infection by day 30, defined as new-onset fever, cough, or dyspnea and either a positive SARS-CoV-2 polymerase chain reaction test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected). RESULTS: Study enrollment closed before full accrual due to recruitment challenges. The primary end point occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6-0.9%, P = 0.20) was identified nor any significant safety issues. CONCLUSION: Oral HCQ taken as prescribed appeared safe among HCWs. No significant clinical benefits were observed. The study was not powered to detect a small but potentially important reduction in infection. TRIAL REGISTRATION: NCT04334148.

Racial/Ethnic Disparities in Healthcare Worker Experiences During the COVID-19 Pandemic: An Analysis of the HERO Registry.

Background: The extent to which healthcare worker (HCWs) experiences during the COVID-19 pandemic vary by race or ethnicity after adjustment for confounding factors is not currently known. Methods: We performed an observational prospective cohort study of 24,769 healthcare workers from 50 U.S. states and the District of Columbia, enrolled between April 10, 2020 and June 30, 2021, and evaluated participant experiences during the COVID-19 pandemic, including testing, diagnosis with COVID-19, emotional experiences, burnout, and interest in vaccines and vaccine clinical trials. Findings: After adjustment for professional role, medical history, and community characteristics, Black and Asian participants were less likely to receive SARS-CoV-2 viral testing (adjusted odds ratio (aOR) 0·82 [0·70, 0·96], p=0·012 and aOR 0·77 [0·67, 0·89], p<0·001 respectively) than White participants. Hispanic participants were more likely to have evidence of COVID-19 infection (aOR 1·23 (1·00, 1·50, p=0·048). Black and Asian participants were less likely to report interest in a COVID-19 vaccine (aOR 0·11 [0·05, 0·25], p<0·001 and aOR 0·48 [0·27, 0·85] p=0·012). Black participants were less likely to report interest in participating in a COVID-19 vaccine trial (aOR = 0·39 [0·28, 0·54], p<0·001). Black participants were also less likely to report 3 or more daily emotional impacts of COVID-19 (aOR = 0·66 [0·53, 0·82], p=<0·001). Black participants were additionally less likely to report burnout (aOR = 0·66 ([0·49, 0·95], p=0·025). Interpretation: In a large, national study of healthcare workers, after adjustment for individual and community characteristics, race/ethnicity disparities in COVID-19 outcomes persist. Future work is urgently needed to understand precise mechanisms behind these disparities and to develop and implement targeted interventions to improve health equity for healthcare workers. Funding: This work was funded by the Patient-Centered Outcomes Research Institute (PCORI), Contract # COVID-19-2020-001.

Design of the Healthcare Worker Exposure Response and Outcomes (HERO) research platform.

BACKGROUND: The SARS CoV-2 virus has caused one of the deadliest pandemics in recent history, resulting in over 170 million deaths and global economic disruption. There remains an urgent need for clinical trials to test therapies for treatment and prevention. DESIGN: An online research platform was created to support a registry community of healthcare workers (HCWs) to understand their experiences and conduct clinical studies to address their concerns. The first study, HERO-HCQ, was a double-blind, multicenter, randomized, pragmatic trial to evaluate the superiority of hydroxychloroquine (HCQ) vs placebo for pre-exposure prophylaxis (PrEP) of COVID-19 clinical infection in HCWs. Secondary objectives were to assess the efficacy of HCQ in preventing viral shedding of COVID-19 among HCWs and to assess the safety and tolerability of HCQ. METHODS: HCWs joined the Registry and were pre-screened for trial interest and eligibility. Trial participants were randomized 1:1 to receive HCQ or placebo. On-site baseline assessment included a COVID-19 nasopharyngeal PCR and blood serology test. Weekly follow-up was done via an online portal and included screening for symptoms of COVID-19, self-reported testing, adverse events, and quality of life assessments. The on-site visit was repeated at Day 30. DISCUSSION: The HERO research platform offers an approach to rapidly engage, screen, invite and enroll into clinical studies using a novel participant-facing online portal interface and remote data collection, enabling limited onsite procedures for conduct of a pragmatic clinical trial. This platform may be an example for future clinical trials of common conditions to enable more rapid evidence generation.

The Optimising Cardiac Surgery ouTcOmes in People with diabeteS (OCTOPuS) randomised controlled trial to evaluate an outpatient pre-cardiac surgery diabetes management intervention: a study protocol.

INTRODUCTION: Cardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to better postoperative outcomes. We previously demonstrated the feasibility of delivering the Optimising Cardiac Surgery ouTcOmes in People with diabeteS (OCTOPuS) intervention, an outpatient intervention delivered by diabetes healthcare professionals for people with suboptimally managed diabetes over 8-12 weeks before elective cardiac surgery. The present study will assess the clinical and cost-effectiveness of the intervention in cardiothoracic centres across the UK. METHODS AND ANALYSIS: A multicentre, parallel group, single-blinded 1:1 individually randomised trial comparing time from surgery until clinically fit for discharge in adults with suboptimally managed type 1 diabetes or type 2 diabetes undergoing elective surgery between the OCTOPuS intervention and usual care (primary endpoint). Secondary endpoints will include actual time from surgery to discharge from hospital; days alive and either out of hospital or judged as clinically fit for discharge; mortality; time on intensive therapy unit (ITU)/ventilator; infections; acute myocardial infarction; change in weight; effect on postoperative renal function and incidence of acute kidney injury; change in HbA1c; frequency and severity of self-reported hypoglycaemia; operations permanently cancelled for suboptimal glycaemic levels; cost-effectiveness; psychosocial questionnaires. The target sample size will be 426 recruited across approximately 15 sites. The primary analysis will be conducted on an intention-to-treat population. A two-sided p value of 0.05 or less will be used to declare statistical significance for all analyses and results will be presented with 95% CIs. ETHICS AND DISSEMINATION: The trial was approved by the South Central-Hampshire A Research Ethics Committee (20/SC/0271). Results will be disseminated through conferences, scientific journals, newsletters, magazines and social media. TRIAL REGISTRATION NUMBER: ISRCTN10170306.

Impact of the Early Phase of the COVID-19 Pandemic on US Healthcare Workers: Results from the HERO Registry.

BACKGROUND: The HERO registry was established to support research on the impact of the COVID-19 pandemic on US healthcare workers. OBJECTIVE: Describe the COVID-19 pandemic experiences of and effects on individuals participating in the HERO registry. DESIGN: Cross-sectional, self-administered registry enrollment survey conducted from April 10 to July 31, 2020. SETTING: Participants worked in hospitals (74.4%), outpatient clinics (7.4%), and other settings (18.2%) located throughout the nation. PARTICIPANTS: A total of 14,600 healthcare workers. MAIN MEASURES: COVID-19 exposure, viral and antibody testing, diagnosis of COVID-19, job burnout, and physical and emotional distress. KEY RESULTS: Mean age was 42.0 years, 76.4% were female, 78.9% were White, 33.2% were nurses, 18.4% were physicians, and 30.3% worked in settings at high risk for COVID-19 exposure (e.g., ICUs, EDs, COVID-19 units). Overall, 43.7% reported a COVID-19 exposure and 91.3% were exposed at work. Just 3.8% in both high- and low-risk settings experienced COVID-19 illness. In regression analyses controlling for demographics, professional role, and work setting, the risk of COVID-19 illness was higher for Black/African-Americans (aOR 2.32, 99% CI 1.45, 3.70, p < 0.01) and Hispanic/Latinos (aOR 2.19, 99% CI 1.55, 3.08, p < 0.01) compared with Whites. Overall, 41% responded that they were experiencing job burnout. Responding about the day before they completed the survey, 53% of participants reported feeling tired a lot of the day, 51% stress, 41% trouble sleeping, 38% worry, 21% sadness, 19% physical pain, and 15% anger. On average, healthcare workers reported experiencing 2.4 of these 7 distress feelings a lot of the day. CONCLUSIONS: Healthcare workers are at high risk for COVID-19 exposure, but rates of COVID-19 illness were low. The greater risk of COVID-19 infection among race/ethnicity minorities reported in the general population is also seen in healthcare workers. The HERO registry will continue to monitor changes in healthcare worker well-being during the pandemic. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04342806.