Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04347798 |
| Other study ID # |
Pro00100000 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 1, 2020 |
| Est. completion date |
June 30, 2022 |
Study information
| Verified date |
March 2023 |
| Source |
University of Alberta |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
This study aims to evaluate the experience of Alberta patients with inflammatory arthritis
who participate in the the RAPPORT-ONTRAAC registry during the COVID-19 pandemic,
specifically comparing the experience of those taking anti-malarial medications compared to
those who do not. This registry includes approximately 2500 northern Alberta patients with
inflammatory arthritis who receive highly complex therapies which may be associated with side
effects. This program of data collection and research has been evaluating the effectiveness
and safety as well as associated health care costs of rheumatoid and psoriatic arthritis
patients since 2004. The principle investigators are based at the University of Alberta while
the co-investigators are academic rheumatologists at the University of Alberta. The registry
has approximately 900 patients taking anti-malarials combined with their complex therapies
and ~ 1500 not on anti-malarials in combination with their complex therapies. We aim to
perform a case control study evaluating the impact of anti-malarial drugs (eg.
hydroxychloroquine and chloroquine) on the development of COVID-19 compared to those patients
who are not on anti-malarial drugs over the next 6-12 months. In addition to frequent e-mail
surveys screening for the clinical symptoms of COVID-19 and understanding their concomitant
arthritis medication use, we will compare the healthcare outcomes of both groups of arthritis
patients with and without COVID-19 for the duration of the pandemic. This information will
provide critical information beyond an anecdotal level on whether or not anti-malarials truly
provide a protective benefit against COVID-19 or reduce the severity of infection. A blood
sample from all participants (Covid-19 positive and negative) will be drawn approximately six
months into the study for measurement of antibodies to Covid-19 and possible blood types and
HLA alleles. Additionally, this study will be linked to another study "Persistence of
SARS-Cov2 in immunocompromised patients" which will specifically evaluate COVID-19 serology
and nasopharyngeal swab findings in the subset of patients who develop COVID-19.
Description:
PURPOSE:
1. To evaluate the impact of anti-malarial medications (hydroxychloroquine and chloroquine)
on the development and severity of COVID-19 infection during the current COVID-19
pandemic in an inception cohort registry of northern Alberta rheumatoid and psoriatic
arthritis patients who are on complex biologic therapies for the duration of the
pandemic.
2. To further evaluate the impact of all biologic medications currently in the registry on
the development and severity of COVID-19 by mechanism of action (eg. TNF antagonism vs
IL-6 blockade, etc).
HYPOTHESIS: We hypothesize that the "case" group of patients on concomitant anti-malarial
treatment with their biologic agent will have a lower incidence and severity of COVID-19
infection compared to those not on anti-malarials based on anecdotal reports of efficacy of
anti-malarials on COVID-19 infection from international reports.
JUSTIFICATION: The COVID-19 pandemic has introduced unforeseen challenges internationally and
led to great uncertainty for patients who are immunocompromised, such as patients in the
RAPPORT registry. Recent anecdotal reports from other countries have been associated with
media and political escalation of the potential benefit of anti-malarial drugs on the course
of COVID-19 infection. This has led to threats to the supply of anti-malarials drugs for
patients with rheumatic diseases like lupus and rheumatoid and psoriatic arthritis, where the
benefits are proven. The RAPPORT inception cohort registry provides a unique opportunity to
evaluate the impact of COVID-19 in an immunocompromised population, while also evaluating the
potential impact of possible treatments for COVID-19.
OBJECTIVES:
Primary
1. To evaluate the impact of anti-malarial medications (hydroxychloroquine and chloroquine)
on the development and severity of COVID-19 infection during the current COVID-19
pandemic in an inception cohort registry of northern Alberta rheumatoid and psoriatic
arthritis patients who are on complex biologic therapies for the duration of the
pandemic.
2. To further evaluate the impact of all biologic medications currently in the registry on
the development and severity of COVID-19 by mechanism of action (eg. TNF antagonism vs
IL-6 blockade, etc).
Secondary
1. To evaluate the incidence of COVID-19 versus other infections over the remaining
duration of the pandemic in an immunocompromised population.
2. To compare the incidence of COVID-19 versus other infections over the remaining duration
of the pandemic in the proportion of patients from the RAPPORT registry who take
concomitant anti-malarials versus those patients that do NOT take anti-malarials.
3. To compare the impact of different mechanisms of action of biologic medications within
the RAPPORT registry, on the incidence of COVID-19 versus other infections
RESEARCH METHOD/PROCEDURES:
For this case control study, we have identified ~900 patients within the RAPPORT-ONTRAAC
registry who are taking concomitant anti-malarial medications with their biologic medication
compared to ~ 1500 patients who are NOT taking concomitant anti-malarial medications. The
current consent for the RAPPORT-ONTRAAC registry allows patients to be contacted for their
potential participation in future studies. Based on this consent, we aim to send a letter to
all existing RAPPORT patients inviting them to participate in this study.
This letter will be sent by email to those with an associated email address and by Canada
Post mail for those who do not. Similar to previous surveys we have conducted, the letter
will provide a synopsis of the current situation with the COVID-19 pandemic and request for
the patient to consent to the following: (1) consent to receive email/letters with surveys of
their clinical status at week 0 (the first point of contact), week 2, then every 4 weeks
until the pandemic is over according to the World Health Organization or most appropriate
local declaration and (2) consent to allow the study team access to the patient's medical
health records (Connectcare/Netcare) for the duration of the pandemic to provide complete
information regarding any healthcare utilization, investigations and outcomes over time. The
act of consent will be obtained if the patient answers specifically that the study team can
access their records and by the act of completing the survey every time. We will collect a
blood sample when the pandemic is over from the consenting patients for consideration of
serology testing.
The survey will screen for clinical symptoms of COVID-19 and concomitant status of their
inflammatory arthritis and medication use. This information is linked by a unique identifier
with the RAPPORT-ONTRAAC registry. The RAPPORT-ONTRAAC registry collects baseline, and at
least annual information including patient demographics, ethnicity, disease characteristics,
serologies, and patient-reported outcomes evaluating the impact of arthritis on their
activities of daily living. With the additional linkage to their electronic medical records,
we aim to identify the following: hospitalizations, and laboratory and diagnostic
investigations. Access to the entire cohort's electronic medical records will provide the
opportunity to capture patients who may not develop any symptoms consistent with COVID and/or
may not be keen to participate in ongoing surveys but may be impacted by COVID-19. The subset
of patients who develop COVID-19 will be contacted to participate in the associated study
(Persistence of SARS-CoV2 in immunocompromised patients; Dr. M. Osman) for more in-depth
serological evaluations and nasopharyngeal swabs. At the end of the study, we will collect a
blood sample as well to ensure that COVID-19 serological evaluations are completed on
asymptomatic individuals who participated in the study.
The survey, developed in collaboration with Infectious Disease experts (Drs. Sonpar, Swartz,
Shafran, Singh), will screen for currently recognized signs and symptoms of COVID-19.
Additionally, confirmation of current arthritis medication use including all disease
modifying anti-rheumatic drugs (DMARDS) as well as biologics will be captured. Surveys will
be completed on REDCAP through email link, provided directly on the email or as a hyperlink
that the patient can type in if they receive the survey by Canada Post. The REDCAP survey
will be developed and housed by EPICORE (Epidemiology and Research Coordinating Center).
For the remainder of the pandemic, electronic medical record and NETCARE searches will be
conducted for all consenting patients with pre-specified outcomes and interim investigations
and/or procedures or hospitalizations in Alberta Health Services facilities. REDCAP survey
responses will be collated with these searches.
PLAN FOR DATA ANALYSIS: A response rate of 40% is expected for this study. Descriptive data
analyses will be conducted to describe the population of inflammatory arthritis patients
divided between those who are currently taking an anti-malarial and those who are not. The
registry provides information including demographics (gender, age, ethnicity) and at least
annual disease activity status with validated disease activity scores which differentiate
between low disease activity state/remission and mild, moderate and severe disease activity.
Co-morbidities through the Charlson Comorbidity Index will be identified and compared between
groups. Survey results over the pandemic per patient will be analyzed. Electronic medical
records will be reviewed at least monthly for all consenting patients to identify and
quantify investigations, procedures and healthcare resources utilized during the pandemic.
With multivariate analyses, the impact of anti-malarial use on the development and severity
of COVID-19 will be evaluated between the two groups, adjusting for important confounders
including the following: co-morbidities (eg. cardiac and respiratory diseases, diabetes),
biologic mediations, steroid use and other DMARDs. Further stratification by biologic DMARD
might be conducted. Healthcare utilization between groups will be compared over time.
Quantification of antibodies to Covid-19 will be compared between the anti-malarial and
non-anti-malarial groups.
