Preventive effect of Lianhua Qingwen capsule on close contacts of seasonal influenza in residential environments: protocol for a multicenter, randomized, double-blind, placebo-controlled study

Abstract

Background: Seasonal influenza poses a high risk of death worldwide. Lianhua Qingwen (LHQW) is effective in shortening the time to symptom alleviation in patients with influenza, but there is a lack of convincing clinical trials targeting influenza prevention. This study aims to evaluate both efficacy and safety of LHQW in the preventing spread of seasonal influenza among close contacts under a cluster setting.

Methods: This study is a randomized, double-blind, multicenter clinical trial to evaluate the preventive efficacy and safety of LHQW in close contacts in a residential environments; 1,884 close contacts will be enrolled in this trial at 72 centers in China, with a five-day duration of LHQW or placebo. All participants were randomized into the LHQW and placebo groups in a 1:1 ratio via the interactive web response system (IWRS), balanced by the stochastic minimization method. Participants are required to undergo three visits (on days 3, 5, and 9 after initiation of medication). At each visit, a throat swab is collected from the participant, and RT-PCR is used to detect influenza virus nucleic acid. Symptom scoring will be performed nightly for the duration of the trial. The primary efficacy outcome was the secondary infection risk in close contacts on day 9 (±1) after medication. Safety outcomes are the incidence and severity of adverse events. This study used a randomized, double-blind, multicenter design method to evaluate the efficacy and safety of LHQW for close contacts in a congregate setting with risks of seasonal influenza transmission, to provide a valuable reference for clinical application. The treatment period of this study was five days and 1,884 close contacts were enrolled. All cases were randomized into experimental and placebo groups as index cases, and each subject returned three times during the treatment period on days 3, 5 and 9 after drug or placebo treatment, respectively, and the corresponding examinations were performed to evaluate the effect of the drug. Symptom scoring will be performed nightly for the duration of the trial.

Discussion: This trial is the first seasonal influenza prevention study of traditional Chinese medicines concerning prophylactic effects globally. Positive findings could demonstrate the efficacy of LHQW against seasonal influenza, which provides a new therapeutic option for infection prevention, symptom alleviation, cost reduction, and renewal of treatment guideline.

Trial registration: The trial has been registered at Chinese Clinical Trial Registry (ChiCTR2300074385).

Keywords: Lianhua Qingwen (LHQW); clinical trial; influenza; preventive effect; residential environment.

Figure 1

Flow chart. The study period consists of a screening period and a visit period, lasting a total of 30 days. Subjects will be randomly assigned to either the trial or control group after meeting the inclusion/exclusion criteria at screening. The screening window is 2 days, day 0 is the day of enrollment, and the day of drug initiation is “day 1”, randomization and drug initiation can be on the same day, with a total of 5 days of dosing, and subjects will be visited on days the 3rd, 5th, and 9th after dosing to complete the relevant examinations, with a window of 1 day for the visit. Indicated cases were followed up by telephone on day five to document their co-administration of medication, with a follow-up window of one day. Close contacts were followed up by telephone on day 30 to collect economics data, with a follow-up window of 3 days.

Figure 2

Inclusion criteria for indicated cases and close contacts. Clustered unit is defined as shared living environments, including the same family, the same school dormitory, the same factory dormitory, and the same shared unit, among others.