The HERO Research Program sought to engage healthcare workers (HCWs) in research to understand the impact of COVID-19 on their health.
The first part of this effort, the national registry, identified and enrolled a large number of healthcare workers (HCWs) who worked on the front lines of the coronavirus pandemic and were at risk for developing COVID-19 infection. HCWs who chose to join the registry had the option of providing health information about relevant COVID-19 risk factors, medical encounters, and health status.
The second part of the project was a randomized clinical trial to look at whether hydroxychloroquine (HCQ) can be used effectively to prevent COVID-19 infections in HCWs. The research team identified and sought consent from HCWs enrolled in the registry who expressed interest in participating in the clinical trial.
Results of the second part of the HERO Research Program, the randomized clinical trial, are posted below. The results of the first part of the program, the national registry, will be released in 2023.
HERO Registry
The national registry identified and enrolled a large number of HCWs who worked on the front lines of the coronavirus pandemic and were at risk for developing COVID-19 infection. HCWs who chose to join the registry had the option of providing health information about relevant COVID-19 risk factors, medical encounters, and health status.
The results from the national registry component of this project will be released in 2023.
HERO-HCQ Trial: Does Hydroxychloroquine Prevent COVID-19 Infection in Healthcare Workers?
View the... Professional Abstract | Peer Review Summary | Final Research Report
Results Summary
Download Summary Español (pdf) Audio Recording (mp3)
What was the research about?
Healthcare workers are at high risk for getting COVID-19 while caring for patients. Early in the pandemic, laboratory studies showed that a medicine called hydroxychloroquine, or HCQ, might prevent COVID-19.
In this study, the research team wanted to learn if taking HCQ was safe and prevented COVID-19 in healthcare workers. First, the team did a study comparing HCQ to placebo. A placebo is a pill without active ingredients. Using a placebo helps researchers learn if results are due to a medicine or chance. Then the team did a meta-analysis. The meta-analysis combined results from this study and four others comparing HCQ versus placebo. Combining data from multiple studies provides stronger results than just looking at single studies.
What were the results?
HCQ was safe but didn’t prevent COVID-19 infection.
In the study, the proportion of healthcare workers who got COVID-19 was similar between those taking HCQ versus placebo. In terms of safety, the number of adverse events didn’t differ between those taking HCQ versus placebo after two months. An adverse event is when medical care causes harm, such as an abnormal heart rhythm.
The meta-analysis had similar results. The risk of COVID-19 infection and adverse events didn’t differ between healthcare workers taking HCQ versus placebo.
Who was in the study?
The study included 1,359 healthcare workers who were potentially exposed to COVID-19 at work. Of these, 91 percent were White, and 6 percent were Hispanic or Latino. The average age was 44, and 65 percent were women.
The meta-analysis included 3,672 people from this study and four others in the United States and Mexico. The people were healthcare workers and others at high risk, like their household contacts.
What did the research team do?
Between April and November 2020, the research team recruited healthcare workers from the HERO Registry and from 34 PCORnet® sites. PCORI funded the HERO registry to support research that looks at experiences of healthcare workers during the pandemic. The team assigned workers by chance to receive HCQ or placebo once a day for 30 days.
Healthcare workers completed surveys when they started the study, weekly for three weeks, and again at one month and two months. The surveys asked if workers had taken COVID-19 tests or had symptoms of COVID-19. On days 1 and 30, healthcare workers had COVID-19 PCR and antibody tests.
For the meta-analysis, the research team analyzed data from the five studies together.
Healthcare workers and a patient helped design and conduct the study.
What were the limits of the study?
Fewer healthcare workers enrolled in the study than planned, making it hard to find differences in COVID-19 rates. Because COVID-19 testing was scarce early in the pandemic, the research team included results for suspected and confirmed COVID-19 cases.
Future research could test other ways to prevent COVID-19 in healthcare workers.
How can people use the results?
Health systems can use the results when considering ways to prevent COVID-19 infection in healthcare workers. The methods used in this study can provide examples for researchers working to design research during a pandemic.
Professional Abstract
Objective
To compare the safety and effectiveness of hydroxychloroquine versus placebo in preventing COVID-19 infection in healthcare workers
Study Design
| Design Element | Description |
|---|---|
| Study Design |
RCT Meta-analysis |
| Population |
RCT: 1,359 healthcare workers ages 18 or older with potential workplace exposure to patients with COVID-19 between April and November 2020 Meta-analysis: 3,672 adults with potential workplace exposure to people with COVID-19 through their role as a healthcare worker or public transit worker, or potential exposure as a household contact of a healthcare worker |
| Interventions/ Comparators |
|
| Outcomes |
Primary: confirmed clinical infection with COVID-19 based on positive PCR test or suspected clinical infection with COVID-19 based on new onset of fever, cough, or dyspnea Secondary: viral shedding confirmed by PCR test; serious adverse events; and adverse events of special interest including fever, ventricular arrhythmia, psychosis, angioedema, prolonged QT interval, secondary bacterial infection, and suicidal ideation |
| Timeframe | 60-day follow-up for primary outcome |
This double-blind, randomized controlled trial (RCT) and meta-analysis compared the effectiveness of prophylaxis with hydroxychloroquine versus placebo in preventing COVID-19 infection among healthcare and other at-risk workers. To evaluate the safety and tolerability of hydroxychloroquine, researchers analyzed adverse events.
To recruit healthcare workers, researchers worked with 34 PCORnet® sites and the Healthcare Worker Exposure Response and Outcomes (HERO) registry. In early 2020, PCORI funded the HERO registry to support research exploring the experiences and outcomes of healthcare workers during the COVID-19 pandemic.
In this trial, researchers randomized healthcare workers to receive hydroxychloroquine or placebo for 30 days. Healthcare workers in both arms took the same number of tablets each day.
The trial included 1,359 healthcare workers who had potential exposure to patients with COVID-19 between April and November 2020. Among healthcare workers, 91% were White and 6% were Hispanic or Latino. The average age was 44, and 65% were female.
Healthcare workers completed questionnaires at baseline, weekly for 3 weeks, and after 30 and 60 days. Questionnaires asked if healthcare workers tested positive for or received a diagnosis of COVID-19, or if they had a suspected infection based on symptoms. Healthcare workers had COVID-19 PCR and antibody tests collected through nasal swabs and blood samples at baseline and on day 30.
Because of low enrollment in this trial and other RCTs, researchers also completed a meta-analysis evaluating the safety and efficacy of hydroxychloroquine prophylaxis for COVID-19. The meta-analysis included data from 3,672 people participating in this trial and four other RCTs in the United States and Mexico.
Diverse types of healthcare workers and a patient helped design and conduct the study.
Results
RCT. The proportion of healthcare workers who reported a COVID-19 infection did not differ significantly between the two study arms (6% with hydroxychloroquine versus 7.8% with placebo, estimated difference -1.8%; 95% confidence interval: -4.6%, 0.9%).
At 30 days, two healthcare workers without symptoms in each group had confirmed viral shedding. At 60 days, the number of serious adverse events and adverse events of special interest was similar between the two groups.
Meta-analysis. The risk of COVID-19 infection and the risk for adverse events did not differ significantly among healthcare workers who received hydroxychloroquine versus placebo.
Limitations
Researchers enrolled less than 10% of the planned number of healthcare workers; as a result, the RCT was underpowered to detect differences in outcomes among healthcare workers who took hydroxychloroquine versus placebo. Because COVID-19 testing was scarce at the start of the COVID-19 pandemic, researchers included outcomes of both suspected and confirmed infections in the RCT.
Conclusions and Relevance
In this RCT and meta-analysis of healthcare workers exposed to COVID-19, hydroxychloroquine was safe but did not prevent COVID-19 infection compared with placebo.
Future Research Needs
Future research could evaluate other options for prophylactic prevention of COVID-19 in healthcare workers.
| How this project fits under PCORI’s Research Priorities The PCORnet® Study reported in this results summary was conducted using PCORnet®, the National Patient-Centered Clinical Research Network. PCORnet® is intended to improve the nation’s capacity to conduct health research, particularly comparative effectiveness research (CER), efficiently by creating a large, highly representative network for conducting clinical outcomes research. PCORnet® has been developed with funding from the Patient-Centered Outcomes Research Institute® (PCORI®). PCORI identified COVID-19 as an important research topic. Patients, clinicians, and others wanted to learn: What are effective ways to prevent or reduce the impact of COVID-19, especially on vulnerable populations and the healthcare workforce? To help answer this question, PCORI launched an initiative in 2020 to Strengthen Understanding of COVID-19 Impact and Inform Healthcare Responses. The initiative funded this research project and others. |
Peer Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- The reviewers were concerned that the researchers were too restrictive in their choice of studies to include in their meta-analysis of preexposure prophylactic use of hydroxychloroquine (HCQ) to prevent COVID-19 infection in healthcare workers. The researchers responded by describing in the discussion two meta-analyses of postexposure use of the drug to prevent COVID-19 infection in individuals exposed to someone with the illness that also demonstrated no beneficial effect of HCQ for COVID-19 prevention. The researchers used this as evidence that distinguishing between pre- and postexposure studies was unlikely to make a difference in the study results.
- The reviewers asked about the researchers’ conclusions that HCQ has no prophylactic effect on COVID-19, and whether it was based on the underpowered research studies conducted or on the meta-analyses of these research studies. The researchers explained that they based these conclusions on the meta-analyses that confirmed the results of this study.
- The reviewers questioned the study’s sample size, stating that the sample was not large enough to answer any clinical questions. The researchers disagreed with this interpretation, stating that when the study was designed the COVID-19 pandemic was just starting and they did not yet know the actual risk of infection to healthcare workers or the potential for other medical options such as vaccinations to become more prominent. As the pandemic evolved, the researchers revised their sample estimates and eventually stopped enrollment before meeting their sample size goal because of growing evidence that HCQ would not be an important prophylactic treatment for COVID-19.
Final Research Report
View this project's final research report.
10.25302/08.2022.COVID.192020001
More to Explore...
Related News (April 13, 2020)
DCRI-Led Registry Launches, Invites Healthcare Workers Nationwide to Fight COVID-19 Together