Covid-19 Living Data

Trial NCT05303584
Publication Tang R, Lancet Resp Med, 2023
Dates: 2022-04-23 to 2022-05-23
Funding: Mixed (National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. Jin-Bo Gou, Haitao Huang, Xiaolong Li, Xue Wang, Peng Wan and Tao Zhu are employees of CanSino Biologics. Tao Zhu owns stock in CanSino Biologics. )
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / China Follow-up duration (months): 0.9
	Inhaled Ad5-nCoV 1.0x10^10 vp (n = 117) IM Ad5-nCoV 5.0x10^10 vp (n = 120) 3 mcg CoronaVac (n = 119)
Inclusion criteria	Healthy male or female adults aged 18 years or older who had completed three doses of vaccination with inactivated COVID-19 vaccines at least 6 months before can provide with informed consent and sign informed consent form (ICF) able to and willing to comply with the requirements of the clinical trial program and could complete the 6-month follow-up of the study.
Exclusion criteria	Have the medical history or family history of convulsion, epilepsy, encephalopathy and psychosis Be allergic to any component of the research vaccines, or used to have a history of hypersensitivity or serious reactions to vaccination Vaccine-related SAE occurred after previous vaccination with COVID-19 vaccine Women with positive urine pregnancy test or in lactation Have acute febrile diseases or infectious diseases or have a history of SARS Axillary temperature>37.0C Have serious cardiovascular diseases, such as arrhythmia, conduction block, myocardial infarction, severe hypertension that cannot be controlled by medication (systolic blood pressure ≥180mmHg and/or diastolic blood pressure ≥110mmHg when measured in the field) Have severe chronic diseases or condition is not stable, such as asthma, diabetes, thyroid disease Congenital or acquired angioedema / neuroedema Have the history of urticaria 1 year before Have asplenia or functional asplenia Patients with chronic obstructive pulmonary disease, pulmonary fibrosis and other pulmonary abnormalities Have history of SARS-CoV-2 infection or COVID-19 Have symptoms of upper respiratory tract infection Have traveled to medium or high risk areas or traveled abroad in the past 21 days, and epidemiologically contacted with SARS-CoV-2 Any medical, psychological, social, or other conditions that, in the investigator's judgment, are inconsistent with the protocol or affect the subject's informed consent.
Interventions
	Intervention 1 IN dose of 1.0x10^10 vp in 0.1 ml of aerosolised Ad5-nCoV (2nd booster), at least 6 months (median 6.6) after 3 doses of Coronovac. 1 IM dose of 5.0x10^10 vp in 0.5 ml of Ad5-nCoV (2nd booster), at least 6 months (median 6.6) after 3 doses of Coronovac.
	Control 1 IM dose of 3 mcg of Coronovac (2nd booster), at least 6 months (median 6.6) after 3 doses of Coronovac.
Participants
	Randomized 356 participants
	Characteristics of participants Type of participants: Healthy adults N=356 155 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR
	Description of participants Healthy adults previously in receipt of 3 doses of CoronaVac and with no history of SARS-CoV-2/COVID-19 in multiple centres in China.
Primary outcome
	In the register 1. Incidence of adverse reactions within 28 days after the booster dose [Time Frame: Within 28 days the booster dose]. 2. GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose [Time Frame: On day 28 after the booster dose].
	In the report 1. Incidence of adverse reactions occurring within 28 days after the fourth dose. 2. Geometric mean titres (GMTs) for neutralizing antibodies against the live SARS-CoV-2 virus at day 28.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes Data accessibility: All data will be made available from the corresponding author upon reasonable request. All code used to produce the results will be made available from the corresponding author upon reasonable request. Correspondence to: Hua Hou PhD, houlihua@sina.com; Or Prof Feng-Cai Zhu, jszfc@vip.sina.com; Or Prof Jing-Xin Li, jingxin42102209@126.com
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print article, the study registry was used in data extraction and risk of bias assessment. Neither protocol, statistical analysis plan nor supplementary appendices were available at the time of extraction. Preliminary analysis, follow-up visits were scheduled up to 6 months after 2nd booster; follow-up after 28 days reported here. The target sample size specified in the registry was achieved. Some outcomes are only reported in figures wihtout complete numbers (e.g., Ab GMT). There is no change from the trial registration in the interventions and control treatments. Report is unclear regarding crossover: "The analysis was based on the modified full-analysis cohort, with some participants reclassified into the correct groups according to the vaccines that they received". This trial was updated on Mars 28th, 2023 after publication of the study report.