TY - JOUR
T1 - Proactive prophylaxis with azithromycin and hydroxychloroquine in hospitalized patients with COVID-19 (ProPAC-COVID)
T2 - a statistical analysis plan
AU - Sivapalan, Pradeesh
AU - Ulrik, Charlotte Suppli
AU - Lappere, Therese Sophie
AU - Eklöf, Josefin Viktoria
AU - Shaker, Saher Burhan
AU - Bødtger, Uffe Christian Steinholtz
AU - Browatzki, Andrea
AU - Meyer, Christian Niels
AU - Weinreich, Ulla Møller
AU - Laursen, Christian B.
AU - Biering-Sørensen, Tor
AU - Knop, Filip Krag
AU - Lundgren, Jens D.
AU - Jensen, Jens Ulrik Stæhr
PY - 2020
Y1 - 2020
N2 - Background: There is an urgent need for treatments that can shorten hospitalization and lower the risk of secondary infection and death in patients with corona disease. The ProPac-COVID trial evaluates whether combination therapy with macrolide azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy, and pre-emptive treatment of supra-infections can shorten hospitalization duration and reduce the risk of non-invasive ventilation, treatment in the intensive care unit, and death in patients with acute hospital admission and a positive test for 2019-nCoV and symptoms of COVID-19 disease. Methods: The ProPAC-COVID is a multi-center, randomized, placebo-controlled, double-blinded clinical trial. The primary outcome is number of days spent alive and out of hospital within 14 days from randomization. Randomization will be in blocks of unknown size, and the final allocation will be stratified for age, site of recruitment, and whether the patient has any chronic lung diseases. Data is analyzed using intention-to-treat (ITT) principles, and main analyses will also be subject to modified ITT analysis and per protocol analysis. Discussion: This paper describes the detailed statistical analysis plan for the evaluation of primary and secondary endpoints of the ProPAC-COVID study. Enrolment of patients to the ProPAC-COVID study is still ongoing. The purpose of this paper is to provide primary publication of study results to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. Trial registration: ClinicalTrials.gov NCT04322396. Registered on 26 March 2020.
AB - Background: There is an urgent need for treatments that can shorten hospitalization and lower the risk of secondary infection and death in patients with corona disease. The ProPac-COVID trial evaluates whether combination therapy with macrolide azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy, and pre-emptive treatment of supra-infections can shorten hospitalization duration and reduce the risk of non-invasive ventilation, treatment in the intensive care unit, and death in patients with acute hospital admission and a positive test for 2019-nCoV and symptoms of COVID-19 disease. Methods: The ProPAC-COVID is a multi-center, randomized, placebo-controlled, double-blinded clinical trial. The primary outcome is number of days spent alive and out of hospital within 14 days from randomization. Randomization will be in blocks of unknown size, and the final allocation will be stratified for age, site of recruitment, and whether the patient has any chronic lung diseases. Data is analyzed using intention-to-treat (ITT) principles, and main analyses will also be subject to modified ITT analysis and per protocol analysis. Discussion: This paper describes the detailed statistical analysis plan for the evaluation of primary and secondary endpoints of the ProPAC-COVID study. Enrolment of patients to the ProPAC-COVID study is still ongoing. The purpose of this paper is to provide primary publication of study results to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. Trial registration: ClinicalTrials.gov NCT04322396. Registered on 26 March 2020.
KW - Azithromycin
KW - Detailed statistical analysis plan
KW - Hydroxychloroquine
KW - Infectious diseases
KW - Intervention
KW - Randomized controlled trial
KW - Safety
U2 - 10.1186/s13063-020-04795-0
DO - 10.1186/s13063-020-04795-0
M3 - Journal article
C2 - 33081817
AN - SCOPUS:85092898846
VL - 21
JO - Trials
JF - Trials
SN - 1745-6215
IS - 1
M1 - 867
ER -