MESSAGE
| DATE | 2020-10-07 |
| FROM | Ruben Safir
|
| SUBJECT | Subject: [Hangout - NYLXS] Efficacy and Safety of Hydroxychloroquine vs
|
Although this is only a single study, it would seem to be correctly done
and closes the door on the use of HDQN usage prophylacticly, which would
be the correct usage of the drug according to its method of activity and
modality for other viruses.
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Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure
SARS-CoV-2 Prophylaxis Among Health Care Workers
Benjamin S. Abella, MD, MPhil1; Eliana L. Jolkovsky, BA1; Barbara T.
Biney, MPH1; et al
31-39 minutes
Key Points
Question Does a regimen of hydroxychloroquine, 600 mg, per day, reduce
the transmission of severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) as a pre-exposure prophylaxis strategy when taken by
hospital-based health care workers?
Finding In this double-blind, placebo-controlled randomized clinical
trial that included 132 participants and was terminated early, there was
not a significant difference in reverse-transcriptase polymerase chain
reaction–confirmed SARS-CoV-2 incidence between hydroxychloroquine and
placebo cohorts.
Meaning Among hospital-based health care workers, daily
hydroxychloroquine did not prevent SARS-CoV-2 infection, although the
trial was terminated early and may have been underpowered to detect a
clinically important difference.
Importance Health care workers (HCWs) caring for patients with
coronavirus disease 2019 (COVID-19) are at risk of exposure to severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our
knowledge, there is no effective pharmacologic prophylaxis for
individuals at risk.
Objective To evaluate the efficacy of hydroxychloroquine to prevent
transmission of SARS-CoV-2 in hospital-based HCWs with exposure to
patients with COVID-19 using a pre-exposure prophylaxis strategy.
Design, Setting, and Participants This randomized, double-blind,
placebo-controlled clinical trial (the Prevention and Treatment of
COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary
urban hospitals, with enrollment from April 9, 2020, to July 14, 2020;
follow-up ended August 4, 2020. The trial randomized 132 full-time,
hospital-based HCWs (physicians, nurses, certified nursing assistants,
emergency technicians, and respiratory therapists), of whom 125 were
initially asymptomatic and had negative results for SARS-CoV-2 by
nasopharyngeal swab. The trial was terminated early for futility before
reaching a planned enrollment of 200 participants.
Interventions Hydroxychloroquine, 600 mg, daily, or size-matched
placebo taken orally for 8 weeks.
Main Outcomes and Measures The primary outcome was the incidence of
SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8
weeks of treatment. Secondary outcomes included adverse effects,
treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency
of QTc prolongation, and clinical outcomes for SARS-CoV-2–positive
participants.
Results Of the 132 randomized participants (median age, 33 years
[range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for
the primary outcome. There was no significant difference in infection
rates in participants randomized to receive hydroxychloroquine compared
with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse
events were more common in participants taking hydroxychloroquine
compared with placebo (45% vs 26%; P = .04); rates of treatment
discontinuation were similar in both arms (19% vs 16%; P = .81). The
median change in QTc (baseline to 4-week evaluation) did not differ
between arms (hydroxychloroquine: 4 milliseconds; 95% CI, −9 to 17; vs
placebo: 3 milliseconds; 95% CI, −5 to 11; P = .98). Of the 8
participants with positive results for SARS-CoV-2 (6.4%), 6 developed
viral symptoms; none required hospitalization, and all clinically recovered.
Conclusions and Relevance In this randomized clinical trial, although
limited by early termination, there was no clinical benefit of
hydroxychloroquine administered daily for 8 weeks as pre-exposure
prophylaxis in hospital-based HCWs exposed to patients with COVID-19.
Trial Registration ClinicalTrials.gov Identifier: NCT04329923
The pandemic triggered by severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) has affected more than 6.8 million people in the US, with
more than 200 000 deaths to date.1,2 The illness caused by the
SARS-CoV-2 virus, coronavirus disease 2019 (COVID-19), has spread
broadly with significant effects on elderly and minority individuals,
those with significant comorbidities, and members of the health care
workforce.3-6 Public health measures to prevent COVID-19 disease have
largely depended on physical distancing, use of facial covers and
personal protective equipment (PPE), and hand hygiene.7 Health care
workers (HCWs) assigned to treating patients with COVID-19 have frequent
potential exposures, raising the question of whether pharmacologic
prophylaxis is warranted.
Medication-based prevention and treatment of COVID-19 have proven
challenging. To our knowledge, to date, only 2 medications,
dexamethasone and remdesivir, have been shown to improve outcomes in
severe COVID-19 disease,8,9 and no treatment has proven effective in
mild to moderate disease. Furthermore, no pharmacologic prophylaxis for
COVID-19 has been established. Given the many HCWs with substantial
COVID-19 exposure worldwide, there is great interest in finding an
effective medication to prevent viral transmission.
Hydroxychloroquine, a 4-aminoquinoline with antimalarial and
antiautophagic properties, has been identified as a possible
prophylactic medication for SARS-CoV-2.10,11 Hydroxychloroquine has been
widely used since its US Food and Drug Administration approval in 1956
for treating systemic lupus erythematosus and is generally well
tolerated, with few long-term adverse effects.12,13 A recent randomized
trial for postexposure COVID-19 prophylaxis with a 5-day course of
hydroxychloroquine did not demonstrate clinical benefit.14 However, the
composite primary outcome measure for this study included symptoms
consistent with infection without laboratory confirmation; most patients
did not have assessment of SARS-CoV-2 infection by reverse-transcriptase
polymerase chain reaction (RT-PCR), raising concerns of type II error
from asymptomatic participants.15 We sought to test the hypothesis that
administering daily hydroxychloroquine would prevent SARS-CoV-2
infection in hospital-based HCWs over 8 weeks of exposure via RT-PCR
testing of nasopharyngeal (NP) swabs and serologic antibody testing from
participants at baseline, 4 weeks, and 8 weeks of treatment.
This single-health system, double-blind placebo-controlled randomized
trial was conducted as the prophylaxis substudy of the Prevention and
Treatment of COVID-19 With Hydroxychloroquine (PATCH) investigations at
2 hospitals within the Penn Medicine system: the Hospital of the
University of Pennsylvania, a 839-bed teaching hospital, and Penn
Presbyterian Medical Center, a 375-bed teaching hospital (Philadelphia,
Pennsylvania). Participation spanned from April 9, 2020, to July 14,
2020, during which both hospitals had uniform policies for HCW use of
PPE (including masks, eyewear, and gowns) as well as patient screening
for COVID-19 symptoms. An independent medical monitor, data safety
monitoring board (DSMB), and COVID-19 trial steering committee provided
oversight of safety and efficacy end points. Electronically signed
informed consent was obtained from all participants via direct
communication with a member of the physician investigative team. Consent
was conducted via an internet document signature program (DocuSign;
DocuSign Inc) that was compliant with US Food and Drug Administration 21
CFR Part 11 regulations for signature verification. Approval for the
study was granted by the University of Pennsylvania institutional review
board. The study protocol and statistical analysis plan are included as
Supplement 1 and Supplement 2, respectively. The protocol and manuscript
were prepared following the Consolidated Standards of Reporting Trials
guidelines for randomized clinical trials.
Health care workers at either study hospital were eligible for inclusion
if they (1) worked 20 hours or more per week in hospital-based units,
(2) had no known history of SARS-CoV-2 infection, and (3) did not have
symptoms suggestive of COVID-19 in the 2 weeks before enrollment,
including cough, fever, or shortness of breath. Physicians, nurses,
certified nursing assistants, emergency technicians, and respiratory
therapists were eligible. Enrollment was focused on staff members in the
emergency department and dedicated COVID-19 units. Exclusion criteria
included history of (1) a positive SARS-CoV-2 test result, (2) allergy
or sensitivity to hydroxychloroquine, (3) glucose-6-phosphate
dehydrogenase deficiency, (4) retinal diseases, such as macular
degeneration or diabetic retinopathy, and (5) substantial cardiac
disease (eg, arrhythmia, congestive heart failure, or coronary disease);
other exclusion criteria are listed in Supplement 1. Demographic
information was obtained from participants directly, including
self-report of race/ethnicity.
Safeguards Against Coercion
Recruitment efforts were made by study investigators who were not in any
direct supervisory role or in the same department as the potential HCW
study participant. The consenting investigator reminded potential
enrollees that the decision to participate would not affect performance
evaluations, career advancement, or other employment-related decisions
made by peers or supervisors.
Group Assignments and Study Medications
Participants were randomized by the Penn Investigational Drug Service
(IDS) in a 1:1 ratio to receive either hydroxychloroquine, 600 mg,
daily, or placebo in blocks of 8 using established randomization
software (SealedEnvelope.com; Clerkenwell Workshops). The IDS staff kept
the randomization assignments concealed from study staff and
investigators until interim analyses. Participants remained masked until
study completion. Participants assigned to the hydroxychloroquine arm
received hydroxychloroquine 200-mg tablets (provided by Sandoz, a
division of Novartis Pharmaceuticals), with instructions to take 3
tablets once a day with food. Participants assigned to the placebo arm
received custom-molded identically sized and shaped microcrystalline
cellulose tablets (prepared for this trial by Temple IDS; Temple
University; Philadelphia, Pennsylvania) and given identical instructions.
Testing and Follow-up Procedures
At the time of randomization (baseline), 4 weeks, and 8 weeks,
participants underwent study-specific NP swab testing for SARS-CoV-2 via
a Clinical Laboratory Improvement Amendments–approved RT-PCR test (Quest
Diagnostics). Study-specific NP swabs were obtained by trained members
of the investigative staff using standard flocked tapered swabs (Quest
Diagnostics) and placed immediately in a viral transport medium on ice
for testing. Participants who developed COVID-19 symptoms were referred
to Penn’s occupational medicine department for an urgent NP swab
independent of the scheduled study procedures. At baseline, 4 weeks, and
8 weeks, serologic testing for 3 antibodies was performed:
anti–nucleocapsid IgG, anti–spike protein receptor-binding domain (RBD)
IgM, and anti-RBD IgG. Electrocardiographic (ECG) assessments were
initially not required for enrollment according to the guidelines of the
American College of Rheumatology for the use of hydroxychloroquine in an
ambulatory population. During study conduct, other reports raised
concerns for possible QT interval prolongation with use of
hydroxychloroquine16; thus, the protocol was amended, and we instituted
a 6-lead ECG evaluation at baseline and 4-week follow-up for
participants using a Bluetooth ECG recorder (AliveCor).
Electrocardiogram results were reviewed by a masked cardiologist study
investigator (M.H.) to quantify corrected QT intervals (QTc) using an
electronic caliper system (EP Calipers, version 2.0; EP Studios Inc).
All enrolled participants were contacted weekly by study coordinators to
review daily pill diaries and adverse event standardized questionnaires.
Any potential adverse events reported to the coordinators were relayed
to study investigators, who then called participants to confirm and
document adverse effects and determine the grade according to the Common
Toxicity Criteria for Adverse Events (version 5.0)17 and the probability
of attribution to study treatment. The highest grade of an adverse event
that was experienced by each participant and deemed possibly related to
the study drug was reported.
The primary outcome was the rate of conversion to SARS-CoV-2–positive
status via NP swab in enrolled participants during the 8 weeks of study
participation. Participants were evaluable for the primary outcome if
they had a negative result for the SARS-CoV-2 PCR test at baseline, took
at least 1 dose of study medication, and had the opportunity to complete
8 weeks of the study. Secondary outcomes included the adverse event
rate, rate of serologic antibody positivity for either nucleocapsid or
spike protein antigens, ECG changes after 4 weeks of treatment, and
clinical outcomes for any participants who became SARS-CoV-2 positive
and/or developed COVID-19 symptoms within the 8-week study period.
Statistical Power and Analysis
With the assumption of a 10% infection rate in the HCW population, we
considered rejecting the null hypothesis if the infection rate was 1%
with hydroxychloroquine treatment. With a planned enrollment of 200
participants (hydroxychloroquine arm and placebo arm, each with 100
participants), a 1-sided z test (α = .05) comparing the infection rates
in the 2 groups would have an 80% power to detect a significant
difference when the difference in the population rates was at least 9%.
The study protocol followed a group sequential design that allowed for 2
interim analyses (after 50 and 100 participants enrolled, respectively)
and permitted findings of early efficacy or futility before trial
completion. Control of error rates was accomplished through the
regulated spending of portions of α and β at each interim analysis and
the final analysis (with a total of 5% and 20% across the trial,
respectively). That pattern of spending was determined a priori during
trial planning; 1-sided cutoff levels for z scores in each direction
were established to determine early significance or futility. An early
futility decision indicates that the infection rates diverge
sufficiently from the original assumptions such that it would be
impossible or extremely unlikely to detect a statistically robust
difference were the trial to continue. For the second interim analysis,
the z score needed to achieve early success was high (2.58),
corresponding to a P value of .005. The z score needed to declare
futility was a more modest value of opposite polarity (−0.27). If the z
score were lower (more negative) than −0.27, futility would be
determined, as it would be very unlikely to achieve significance under
the original assumptions. At each interim analysis, the z score and all
other safety and efficacy data were reported by the study team to the
DSMB, which would recommend continuing or halting the study. Statistical
analyses were conducted using Stata, version 16.1 (StataCorp).
Between April 9, 2020, and July 14, 2020, 139 participants provided
consent (Table 1); the last follow-up assessment was completed August 4,
2020. During this study period, the Philadelphia region, including Penn
Medicine hospitals, experienced a peak of infection rates followed by a
decline in cases (eFigure 1 in Supplement 3). Study accrual mirrored the
peak and decline of infection rate in the area (eFigure 1 and eFigure 2
in Supplement 3). Of the 139 patients who provided consent, 7 (5.0%) did
not meet eligibility criteria; therefore, 132 participants were
randomized. Five participants assigned to receive placebo (including 2
participants with positive test results for SARS-CoV-2 by RT-PCR at
baseline) and 2 participants assigned to receive hydroxychloroquine were
not evaluable for the primary outcome (Figure 1). Thus, 64 participants
in the hydroxychloroquine treatment arm and 61 participants in the
placebo arm were evaluable for the primary outcome (n = 125). The median
age of the study population was 33 years (range, 20-66 years). The HCWs
enrolled were predominantly women (91 [69%]), White (109 [83%]), and
without preexisting medical problems (94 [71%]). Most participants
worked as nurses or physicians in the emergency department (74 [56%]) or
on internal medicine wards dedicated to treating patients with COVID-19
(35 [37%]).
Most of the 125 participants evaluable for the primary end point
completed the study. However, 22 of 125 participants (17.6%)
discontinued study treatment early (eTable 1 in Supplement 3), with
similar discontinuation rates between the hydroxychloroquine (12 of 64
[19%]) and placebo (10 of 61 [16%]) treatment arms (P = .73). All
participants who discontinued treatment were followed for the intended
8-week study period and either agreed to complete the study procedures
or provide information about COVID-19 symptoms and additional testing
performed outside of the study.
The conversion of participants to SARS-CoV-2 positive status was
determined either by study-administered NP swabs conducted at 4 weeks
and 8 weeks or, if the participant developed symptoms, referral to the
occupational medicine department for a NP swab. The rate of COVID-19
positivity (Table 2) was similar in the hydroxychloroquine and placebo
arms (6.3% vs 6.6%; P > .99), with infections occurring throughout the
8-week period. None of the 8 participants with COVID-19 required
hospitalization; all were either asymptomatic or had mild disease and
fully recovered (eTable 2 in Supplement 3).
We conducted 2 preplanned interim analyses to determine if early
termination was warranted because of efficacy or futility (eFigure 3 in
Supplement 3). At the second interim analysis, conducted after 100
participants had completed the 8-week study period, 4 participants
assigned to hydroxychloroquine and 3 participants assigned to placebo
had converted to positive SARS-CoV-2 status, yielding a z score of −0.42
(odds ratio, 0.72), below the lower boundary z = −0.27 for futility.
After reviewing the findings of the second interim analysis, the DSMB
recommended early termination of the study and that the most recently
enrolled participants (n = 3) discontinue study procedures immediately;
32 participants near completion were allowed to finish study procedures.
Serological testing for the presence of anti–spike protein RBD IgM and
IgG and nucleocapsid protein IgG (eTable 3 in Supplement 3) demonstrated
that only 2 participants had anti–nucleocapsid IgG at baseline. Both
participants had a negative SARS-CoV-2 RT-PCR test result, and these
participants did not possess anti–spike protein RBD IgG at baseline. At
the end of the 8 weeks, there were more positive participants treated
with hydroxychloroquine (4 [7.4%]) compared with placebo (2 [3.7%]) who
had an IgG antibody against SARS-CoV-2 (P = .40). All participants who
developed antibodies also converted to SARS-CoV-2 positive status
(eTable 4 in Supplement 3).
At least 1 dose of study medication was taken by 65 participants in each
arm; therefore, these participants were evaluable for adverse events
(Table 3). The mean (SD) percentage of total pill counts prescribed that
were actually taken during study treatment was 97% (8%)
(hydroxychloroquine) and 98% (4%) (placebo). No participants in this
study experienced grade 3 or 4 adverse events on the Common Toxicity
Criteria for Adverse Events scale, hospitalizations, or death. However,
there was a significant increase in any adverse events in the
hydroxychloroquine arm vs placebo (45% vs 26%; P = .03), with increased
diarrhea in participants receiving hydroxychloroquine compared with
placebo (32% vs 12%; P = .01). No cardiac events (eg, syncope and
arrhythmias) were observed. There was no significant difference in the
median of changes in QTc between the hydroxychloroquine and placebo arms
(4 milliseconds; 95% CI, −9 to 17; vs 3 milliseconds; 95% CI, −5 to 11;
Wilcoxon 2-sample t test, P = .98; Figure 2).
Among hospital-based HCWs at high risk of exposure to SARS-CoV-2,
hydroxychloroquine, 600 mg, daily, for 8 weeks did not reduce the
incidence of SARS-CoV-2 infection compared with placebo. Our findings
are consistent with what is to our knowledge the only other randomized
COVID-19 prophylaxis trial published to date.14 In that study, Boulware
et al14 randomized 821 asymptomatic adults to hydroxychloroquine or
placebo following a postexposure prophylaxis strategy in which
participants self-identified as having a significant exposure and were
treated with a 5-day course of hydroxychloroquine or placebo. The
treatment protocol allowed for therapy initiation up to 4 days after
exposure; more than 50% of participants started taking medication 3 to 4
days after exposure. This time variability prompted a critique15 that
delayed initiation of hydroxychloroquine may have missed a key biologic
window to prevent transmission. We elected to follow a pre-exposure
prophylaxis strategy under the presumption that (1) prevention might
depend on the timing of therapy, and (2) clear identification of a true
exposure likely to result in transmission is challenging.
Our study also differed from the work of Boulware et al14 regarding
SARS-CoV-2 testing. Following a pragmatic study design, there was a
paucity of viral testing at either study initiation or at the time of
the primary outcome (laboratory-confirmed transmission or illness
compatible with COVID-19). Fewer than 25% of participants with a
positive primary outcome had laboratory confirmation of SARS-CoV-2.
Thus, participants may have become SARS-CoV-2 positive while remaining
asymptomatic (contributing to type II error), or participants may have
contracted another viral illness resulting in fever or cough that was
not COVID-19 (contributing to type I error). By contrast, in our study,
all participants had baseline SARS-CoV-2 testing and were excluded if
found to have a positive result, and our primary outcome was defined as
laboratory-confirmed SARS-CoV-2 transmission.
Similar to other studies of hydroxychloroquine for either viral
prophylaxis or COVID-19 treatment, we found that the medication was
generally well tolerated, with the exception that patients treated with
hydroxychloroquine, 600 mg, for 8 weeks experienced significantly higher
rates of grade 1 to 2 diarrhea than patients treated with placebo. In
addition, we found no significant differences in cardiac adverse events
between the hydroxychloroquine and placebo groups. Myocardial
inflammation associated with SARS-CoV-2 infection may increase
susceptibility to potential cardiac effects of hydroxychloroquine.18
Therefore, the lack of QTc prolongation or arrythmias in our study’s
cohort cannot be used to infer cardiac safety of hydroxychloroquine for
active COVID-19 treatment. Furthermore, some studies have involved the
combined use of azithromycin, a known QTc-prolonging compound, and
hydroxychloroquine19; azithromycin use was an exclusion criterion in our
investigation.
Prophylaxis studies of infectious diseases are highly sensitive to
disease frequency. In Pennsylvania, daily COVID-19 incidence fell during
the course of enrollment (eFigure 1 in Supplement 3), starting at 14.8
cases per 100 000 population per day on April 9, 2020, and ending at 7.1
cases per 100 000 population per day on July 14, 2020.20 The overall
SARS-CoV-2 infection rate in the study cohort was 6.4%; it is possible
that a study of similar design conducted in a community with higher
disease prevalence might yield a higher HCW infection rate and possibly
more power to detect a prophylactic benefit from hydroxychloroquine.
Alternatively, it is possible that uniform use of PPE and hand hygiene
was sufficiently effective to reduce HCW infection to low levels, as
seen in our study population.
Our study has important limitations. Our study was likely established
with insufficient power. Given the small sample size, we cannot exclude
the possibility of an undetected modest potential prophylactic effect of
hydroxychloroquine. We did not attempt to quantify the frequency of
participant exposure or specific timing of exposures. The cohort largely
comprised young healthy HCWs and thus may not be generalizable to other
populations with increased risk because of advanced age or additional
comorbidities. Both study hospitals were located in Philadelphia and may
not be representative of COVID-19 prevalence and exposure risk in other
geographical areas. We cannot exclude the possibility that a lower or
intermittent dose of hydroxychloroquine would be more effective at
prevention, although a recent preclinical investigation in a COVID-19
macaque model did not find differences in antiviral activity with varied
hydroxychloroquine dosing.21 Ongoing prophylaxis trials using
hydroxychloroquine will be important to address these limitations.22,23
This randomized clinical trial did not detect a reduction in SARS-CoV-2
transmission with prophylactic administration of hydroxychloroquine, and
all participants who did contract SARS-CoV-2 were either asymptomatic or
had mild disease courses with full recoveries. As such, we cannot
recommend the routine use of hydroxychloroquine among HCWs to prevent
COVID-19.
Accepted for Publication: September 15, 2020.
Corresponding Author: Ravi K. Amaravadi, MD, Division of
Hematology-Oncology, 852 BRB 2/3, 421 Curie Blvd, Philadelphia, PA 19104
(ravi.amaravadi-at-pennmedicine.upenn.edu).
Published Online: September 30, 2020. doi:10.1001/jamainternmed.2020.6319
Open Access: This is an open access article distributed under the terms
of the CC-BY License. © 2020 Abella BS et al. JAMA Internal Medicine.
Author Contributions: Drs Abella and Amaravadi had full access to all of
the data in the study and take responsibility for the integrity of the
data and the accuracy of the data analysis.
Concept and design: Abella, Jolkovsky, Hyman, Frank, Nasta, Wiletyo,
Milone, Amaravadi, Vyas.
Acquisition, analysis, or interpretation of data: Abella, Jolkovsky,
Biney, Uspal, Hyman, Hensley, Gill, Vogl, Maillard, Babushok, Huang,
Nasta, Walsh, Wiletyo, Gimotty, Milone, Amaravadi, McGovern, Teng, Vyas,
Balian, Kolansky, Dolan, Oyekanmi, Patel, Abdulhay, Helfer, Mullen,
Tisch, Fiordaliso, McFadden, Gouma, Nunez-Cruz, Doran, Callahan, Gamblin.
Drafting of the manuscript: Abella, Jolkovsky, Gill, Wiletyo, Milone,
Amaravadi, Nunez-Cruz.
Critical revision of the manuscript for important intellectual content:
Abella, Jolkovsky, Biney, Uspal, Hyman, Frank, Hensley, Gill, Vogl,
Maillard, Babushok, Huang, Nasta, Walsh, Wiletyo, Gimotty, Amaravadi,
McGovern, Teng, Vyas, Balian, Kolansky, Dolan, Oyekanmi, Patel,
Abdulhay, Helfer, Mullen, Tisch, Fiordaliso, McFadden, Gouma, Doran,
Callahan, Gamblin.
Statistical analysis: Jolkovsky, Wiletyo, Gimotty, Amaravadi.
Obtained funding: Amaravadi.
Administrative, technical, or material support: Abella, Jolkovsky,
Biney, Uspal, Hyman, Frank, Vogl, Maillard, Babushok, Huang, Nasta,
Walsh, Milone, Amaravadi, McGovern, Teng, Vyas, Balian, Kolansky, Dolan,
Oyekanmi, Patel, Abdulhay, Helfer, Mullen, Fiordaliso, McFadden, Gouma,
Nunez-Cruz, Doran, Callahan, Gamblin.
Supervision: Abella, Jolkovsky, Hensley, Gill, Nasta, Walsh, Milone,
Amaravadi.
Conflict of Interest Disclosures: Dr Frank reports consulting income
from Gilead. Dr Milone reports royalty income from patents licensed to
Novartis that is unrelated to hydroxychloroquine. Dr Amaravadi is the
scientific founder and holds equity in Pinpoint Therapeutics, Inc. He is
coinventor on patents covering autophagy inhibitors for cancer and a
consultant for cancer-related programs at Sprint Biosciences, Deciphera,
and Immunaccel. Dr Abella has received grant funding and honoraria from
Becton Dickinson. No other disclosures were reported.
Funding/Support: This study received philanthropic donations from
Leonard and Madlyn Abramson and Mark and Cecilia Vonderheide.
Role of the Funder/Sponsor: The funding individuals had no role in the
design and conduct of the study; collection, management, analysis, and
interpretation of the data; preparation, review, or approval of the
manuscript; and decision to submit the manuscript for publication.
Additional Authors/Prevention and Treatment of COVID-19 With
Hydroxychloroquine (PATCH) Investigators: Shaun K. McGovern, BS, BSN;
Edith M. Teng, BA; Niraj J. Vyas, MBS; Steve Balian, MD; Jonathan A.
Kolansky, BA; Abby R. Dolan, BA; Kehinde O. Oyekanmi, BS; Jaldhi S.
Patel, BS; Nabil M. Abdulhay, BS; David R. Helfer, BS; Isabelle S.
Mullen, BA; Charlotte F. Tisch, BA; Sarah K. Fiordaliso, BA, BSN; Rachel
McFadden, BA, BSN; Sigrid Gouma, PhD; Selene G. Nunez-Cruz, MS, PhD;
Olivia Doran, BS; Paul L. Callahan, BA; and Sarah Gamblin, BA
(University of Pennsylvania).
Additional Contributions: We thank Madison E. Weirick, BA, Christopher
M. McAllister, BA, and other members of the laboratory of Scott Hensley,
PhD, for completing serological assays (Department of Microbiology,
University of Pennsylvania). We are grateful to Eileen McDonnell,
Elizabeth Moore, CRA, Suzanne Rizio, BS, and Karen Moore for
administrative support (Department of Emergency Medicine, University of
Pennsylvania). We also thank the Penn Medicine health care workers who
volunteered to participate in this investigation. None of these
acknowledged individuals received compensation specific to this study.
Data Sharing Statement: See Supplement 4.
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--
So many immigrant groups have swept through our town
that Brooklyn, like Atlantis, reaches mythological
proportions in the mind of the world - RI Safir 1998
http://www.mrbrklyn.com
DRM is THEFT - We are the STAKEHOLDERS - RI Safir 2002
http://www.nylxs.com - Leadership Development in Free Software
http://www.brooklyn-living.com
Being so tracked is for FARM ANIMALS and extermination camps,
but incompatible with living as a free human being. -RI Safir 2013
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