标题：Efficacy and safety of nelfinavir in asymptomatic and mild COVID-19 patients: a structured summary of a study protocol for a multicenter, randomized controlled trial
摘要：Objectives
The aim of this trial is to evaluate the antiviral efficacy, clinical efficacy, and safety of nelfinavir in patients with asymptomatic and mild COVID-19.
Trial design
The study is designed as a multicenter, open-label, blinded outcome assessment, parallel group, investigator-initiated, exploratory, randomized (1:1 ratio) controlled clinical trial.
Participants
Asymptomatic and mild COVID-19 patients will be enrolled in 10 university and teaching hospitals in Japan. The inclusion and exclusion criteria are as follows:
Inclusion criteria:
Japanese male or female patients aged ≥ 20 years
SARS-CoV-2 detected from a respiratory tract specimen (e.g., nasopharyngeal swab or saliva) using PCR, LAMP, or an antigen test within 3 days before obtaining the informed consent
Provide informed consent
Exclusion criteria:
Symptoms developed ≥ 8 days prior to enrolment
SpO
2 < 96 % (room air)
Any of the following screening criteria:
ALT or AST ≥ 5 × upper limit of the reference range
Child-Pugh class B or C
Serum creatinine ≥ 2 × upper limit of the reference range and creatinine clearance < 30 mL/min
(4)
Poorly controlled diabetes (random blood glucose ≥ 200 mg/dL or HbA1c ≥ 7.0%, despite treatment)
(5)
Unsuitable serious complications based on the assessment of either the principal investigator or the sub-investigator
(6)
Hemophiliac or patients with a marked hemorrhagic tendency
(7)
Severe diarrhea
(8)
Hypersensitivity to the investigational drug
(9)
Breastfeeding or pregnancy
(10)
With childbearing potential and rejecting contraceptive methods during the study period from the initial administration of the investigational drug
(11)
Receiving rifampicin within the previous 2 weeks
(12)
Participated in other clinical trials and received drugs within the previous 12 weeks
(13)
Undergoing treatment for HIV infection
(14)
History of SARS-CoV-2 vaccination or wishes to be vaccinated against SARS-CoV-2
(15)
Deemed inappropriate (for miscellaneous reasons) based on the assessment of either the principal investigator or the sub-investigator
Intervention and comparator
Patients who meet the inclusion criteria and do not meet any of the exclusion criteria will be randomized to either the nelfinavir group or the symptomatic treatment group.
The nelfinavir group will be administered 750 mg of nelfinavir orally, three times daily for 14 days (treatment period). However, if a participant tests negative on two consecutive PCR tests of saliva samples, administration of the investigational drug for that participant can be discontinued at the discretion of the investigators.
The symptomatic treatment group will not be administered the investigational drug, but all other study procedures and conditions will be the same for both groups for the duration of the treatment period. After the treatment period of 14 days, each group will be followed up for 14 days (observational period).
Main outcomes
The primary endpoint is the time to negative conversion of SARS-CoV-2. During the study period from Day 1 to Day 28, two consecutive negative PCR results of saliva samples will be considered as the negative conversion of the virus.
The secondary efficacy endpoints are as follows:
For patients with both asymptomatic and mild disease: area under the curve of viral load, half decay period of viral load, body temperature at each time point, all-cause mortality, incidence rate of pneumonia, percentage of patients with newly developed pneumonia, rate of oxygen administration, and the percentage of patients who require oxygen administration.
For asymptomatic patients: incidence of symptomatic COVID-19, incidence of fever (≥ 37.0 °C for two consecutive days), incidence of cough
For patients with mild disease: incidence of defervescence (< 37.0 °C), incidence of recovery from clinical symptoms, incidence of improvement of each symptom
The secondary safety endpoints are adverse events and clinical examinations.
Randomization
Patients will be randomized to either the nelfinavir group or the symptomatic treatment group using the electric data capture system (1:1 ratio, dynamic allocation based on severity [asymptomatic
