Status: Finalised
First registered on:
03/04/2020
Last updated on:
06/07/2020
1. Study identification
EU PAS Register NumberEUPAS34497
Official titleHydroxychloroquine safety and potential efficacy as an antiviral prophylaxis in light of potential wide-spread use in COVID-19: a multinational, large-scale network cohort and self-controlled case series study
Study title acronym
Study typeObservational study
Brief description of the studyThe overarching objective is to investigate safety and potential efficacy as an antiviral prophylaxis in light of potential wide-spread use in COVID-19
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Centre nameUniversity of Oxford
Centre locationUnited Kingdom
Details of (Primary) lead investigator
Title Professor
Last name Prieto-Alhambra
First name Daniel
Is this study being carried out with the collaboration of a research network?
Yes
OHDSI- Observational Health Data Sciences and Informatics
Other centres where this study is being conducted
Multiple centres
In total how many centres are involved in this Study?7
Columbia University, US
Erasmus MC, Netherlands
SIDIAP, Spain
UCLA, US
Janssen Research and Development, UK
Countries in which this study is being conducted
International study
Germany
Japan
Netherlands
Spain
United Kingdom
United States
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed22/11/201822/11/2018
Start date of data collection01/09/200001/09/2000
Start date of data analysis01/03/202001/03/2020
Date of interim report, if expected14/04/2020
Date of final study report30/05/202030/05/2020
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companies
Charities
Government body
Research councils
EU funding schemeIMI2 - EHDEN100
5. Contact details for enquiries
Scientific Enquiries
Title Professor
Last name Prieto-Alhambra
First name Daniel
Address line 1Botnar Research Cenre
Address line 2Nuffield Orthopaedic Centre
Address line 3Windmill Road
CityOxford
PostcodeOX4 2AP
CountryUnited Kingdom
Phone number (incl. country code)00441865223401
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Professor
Last name Prieto-Alhambra
First name Daniel
Address line 1Botnar Research Cenre
Address line 2Nuffield Orthopaedic Centre
Address line 3Windmill Road
CityOxford
PostcodeOX4 2AP
CountryUnited Kingdom
Phone number (incl. country code)00441865223401
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Single-Constituent (Substance INN)Hydroxychloroquine
Single-Constituent (Substance INN)SULFASALAZINE
Single-Constituent (Substance INN)AZITHROMYCIN
Single-Constituent (Substance INN)AMOXICILLIN
7. Medical conditions to be studied
Medical condition(s)Yes
Rheumatoid arthritis
Additional Medical Condition(s)
Coronavirus
8. Population under study
Age
Adults (18 - 44 years)
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects800000
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Data sources not registered with ENCePP
IQVIA Disease Analyser Germany EMR, Germany
IQVIA Open Claims, United States
Optum, United States
PanTher, United States
CCAE, United States
Sources of data
Administrative database, e.g. claims database
Routine primary care electronic patient registry
11. Scope of the study
What is the scope of the study?
Risk assessment
Effectiveness evaluation
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
To study the safety of hydroxychloroquine and the combination of hydroxychloroquine + azithromycin in terms of severe adverse outcomes. Secondly, to study the association between the use of these medicines and the risk of viral infection/s and pneumonia.
Are there primary outcomes?No
Are there secondary outcomes?No
13. Study design
What is the design of the study?
Cohort study
Self controlled case-series
14. Follow-up of patients
Will patients be followed up?Not applicable/no follow-up
15. Data analysis plan
Please provide a brief summary of the analysis method
All analyses are conducted using an international distributed data network with shared analytical tools. For the comparative cohort analyses, propensity score stratification and calibration using negative control outcomes will be used to minimise observed and unobserved confounding respectively. Cox regression models were fitted to estimate Hazard Ratios according to drug exposure. Secondly, self-controlled case series analyses were used, where Incidence Rate Ratios for on vs off-treatment risk of each of the outcomes is estimated using a modified Poisson regression model, adjusted for age and seasonality.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
18. Study Results
Not submitted
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study
Jennifer C.E Lane, James Weaver, Kristin Kostka, Talita Duarte-Salles, Maria Tereza F. Abrahao, Heba Alghoul, Osaid Alser, Thamir M Alshammari, Patricia Biedermann, Edward Burn, Paula Casajust, Mitch Conover, Aedin C. Culhane, Alexander Davydov, Scott L. DuVall, Dmitry Dymshyts, Sergio Fernández Bertolín, Kristina Fišter, Jill Hardin, Laura Hester, George Hripcsak, Seamus Kent, Sajan Khosla, Spyros Kolovos, Christophe G. Lambert, Johan ver der Lei, Kristine E. Lynch, Rupa Makadia, Andrea V. Margulis, Michael E. Matheny, Paras Mehta, Daniel R. Morales, Henry Morgan-Stewart, Mees Mosseveld, Danielle Newby, Fredrik Nyberg, Anna Ostropolets, Rae Woong Park, Albert Prats-Uribe, Gowtham A. Rao, Christian Reich, Jenna Reps, Peter Rijnbeek, Selva Muthu Kumaran Sathappan, Martijn Schuemie, Sarah Seager, Anthony Sena, Azza Shoaibi, Matthew Spotnitz, Marc A. Suchard, Joel Swerdel, Carmen Olga Torre, David Vizcaya, Haini Wen, Marcel de Wilde, Seng Chan You, Lin Zhang, Oleg Zhuk, Patrick Ryan, Daniel Prieto-Alhambra
medRxiv 2020.04.08.20054551; doi: https://doi.org/10.1101/2020.04.08.20054551https://www.medrxiv.org/content/10.1101/2020.04.08.20054551v2
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documents
DescriptionDocumentLatest version
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
