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Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.
Lancet. 2021 07 17; 398(10296):213-222.Lct

Abstract

BACKGROUND

CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey.

METHODS

This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 μg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting.

FINDINGS

Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6-59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7-261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4-92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001).

INTERPRETATION

CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile.

FUNDING

Turkish Health Institutes Association.

Authors+Show Affiliations

Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey; Hacettepe University Vaccine Institute, Ankara, Turkey.Department of Gastroenterology, Turkish Republic Ministry of Health, İstanbul Provincial Health Directorate, University of Health Sciences İstanbul Ümraniye Training and Research Hospital, İstanbul, Turkey.Department of Infectious Diseases and Clinical Microbiology, Hacettepe University School of Medicine, Ankara, Turkey; Hacettepe University Vaccine Institute, Ankara, Turkey. Electronic address: makova@hacettepe.edu.tr.Department of Infectious Diseases and Clinical Microbiology, Ankara Yıldırım Beyazıt University, Ankara City Hospital, Ankara, Turkey.Department of Infectious Diseases and Clinical Microbiology, Ankara University School of Medicine, Ankara, Turkey.Department of Infectious Diseases and Clinical Microbiology, Kocaeli University School of Medicine, Kocaeli, Turkey.Department of Infectious Diseases, Turkish Republic Ministry of Health, İzmir Provincial Health Directorate, İzmir University of Health Sciences Tepecik Training and Research Hospital, İzmir, Turkey.Department of Infectious Diseases, Turkish Republic Ministry of Health, Ankara Provincial Health Directorate, Ankara Training and Research Hospital, Ankara, Turkey.Department of Infectious Diseases and Clinical Microbiology, Bursa Uludağ University Health Application and Research Centre, Bursa Uludağ University Hospital, Bursa, Turkey.Department of Infectious Diseases and Clinical Microbiology, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey.Department of Infectious Diseases and Clinical Microbiology, Ege University School of Medicine, İzmir, Turkey.Department of Chest Diseases, Turkish Republic Ministry of Health, İzmir Provincial Health Directorate, University of Health Sciences Dr Suat Seren Chest Diseases and Surgery Training and Research Hospital, İzmir, Turkey.Department of Infectious Diseases and Clinical Microbiology, İstanbul University, İstanbul School of Medicine, İstanbul, Turkey.Department of Infectious Diseases and Clinical Microbiology, Akdeniz University School of Medicine, Antalya, Turkey.Department of Infectious Diseases and Clinical Microbiology, Turkish Republic Ministry of Health, İstanbul Provincial Health Directorate, Prof Dr Cemil Taşcıoğlu City Hospital, İstanbul, Turkey.Department of Infectious Diseases and Clinical Microbiology, Acıbadem University Atakent Hospital, İstanbul, Turkey.Department of Infectious Diseases and Clinical Microbiology, Çukurova University Balcalı Hospital Health Application and Research Centre, Adana, Turkey.Department of Infectious Diseases and Clinical Microbiology, Marmara University School of Medicine, İstanbul, Turkey.Department of Infectious Diseases and Clinical Microbiology, Karadeniz Technical University School of Medicine, Trabzon, Turkey; Department of Chest Diseases, Turkish Republic Ministry of Health, Ankara Provincial Health Directorate, Ankara Keçiören Sanatorium, Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital, Ankara, Turkey.Department of Infectious Diseases and Clinical Microbiology, Dicle University School of Medicine, Diyarbakır, Turkey.Department of Chest Diseases, Turkish Republic Ministry of Health, İstanbul Provincial Health Directorate, University of Health Sciences İstanbul Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, İstanbul, Turkey.Department of Infectious Diseases and Clinical Microbiology, Turkish Republic Ministry of Health, Kayseri City Training and Research Hospital, Kayseri, Turkey.Department of Infectious Diseases and Clinical Microbiology, İnönü University Turgut Özal Health Centre, Malatya, Turkey.Department of Infectious Diseases and Clinical Microbiology, Gaziantep University Şahinbey Research and Application Centre, Gaziantep, Turkey.Department of Infectious Diseases and Clinical Microbiology, Karadeniz Technical University School of Medicine, Trabzon, Turkey; Department of Chest Diseases, Turkish Republic Ministry of Health, Ankara Provincial Health Directorate, Ankara Keçiören Sanatorium, Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital, Ankara, Turkey.Department of Virology, Ankara University Faculty of Veterinary Medicine, Ankara, Turkey.Department of Medical Microbiology, Hacettepe University School of Medicine, Ankara, Turkey.Department of Infectious Diseases and Clinical Microbiology, Hacettepe University School of Medicine, Ankara, Turkey; Hacettepe University Vaccine Institute, Ankara, Turkey.No affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34246358

Citation

Tanriover, Mine Durusu, et al. "Efficacy and Safety of an Inactivated Whole-virion SARS-CoV-2 Vaccine (CoronaVac): Interim Results of a Double-blind, Randomised, Placebo-controlled, Phase 3 Trial in Turkey." Lancet (London, England), vol. 398, no. 10296, 2021, pp. 213-222.
Tanriover MD, Doğanay HL, Akova M, et al. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet. 2021;398(10296):213-222.
Tanriover, M. D., Doğanay, H. L., Akova, M., Güner, H. R., Azap, A., Akhan, S., Köse, Ş., Erdinç, F. Ş., Akalın, E. H., Tabak, Ö. F., Pullukçu, H., Batum, Ö., Şimşek Yavuz, S., Turhan, Ö., Yıldırmak, M. T., Köksal, İ., Taşova, Y., Korten, V., Yılmaz, G., ... Unal, S. (2021). Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet (London, England), 398(10296), 213-222. https://doi.org/10.1016/S0140-6736(21)01429-X
Tanriover MD, et al. Efficacy and Safety of an Inactivated Whole-virion SARS-CoV-2 Vaccine (CoronaVac): Interim Results of a Double-blind, Randomised, Placebo-controlled, Phase 3 Trial in Turkey. Lancet. 2021 07 17;398(10296):213-222. PubMed PMID: 34246358.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. AU - Tanriover,Mine Durusu, AU - Doğanay,Hamdi Levent, AU - Akova,Murat, AU - Güner,Hatice Rahmet, AU - Azap,Alpay, AU - Akhan,Sıla, AU - Köse,Şükran, AU - Erdinç,Fatma Şebnem, AU - Akalın,Emin Halis, AU - Tabak,Ömer Fehmi, AU - Pullukçu,Hüsnü, AU - Batum,Özgür, AU - Şimşek Yavuz,Serap, AU - Turhan,Özge, AU - Yıldırmak,Mustafa Taner, AU - Köksal,İftihar, AU - Taşova,Yeşim, AU - Korten,Volkan, AU - Yılmaz,Gürdal, AU - Çelen,Mustafa Kemal, AU - Altın,Sedat, AU - Çelik,İlhami, AU - Bayındır,Yaşar, AU - Karaoğlan,İlkay, AU - Yılmaz,Aydın, AU - Özkul,Aykut, AU - Gür,Hazal, AU - Unal,Serhat, AU - ,, Y1 - 2021/07/08/ PY - 2021/05/18/received PY - 2021/06/10/revised PY - 2021/06/15/accepted PY - 2021/7/12/pubmed PY - 2021/7/31/medline PY - 2021/7/11/entrez SP - 213 EP - 222 JF - Lancet (London, England) JO - Lancet VL - 398 IS - 10296 N2 - BACKGROUND: CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey. METHODS: This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 μg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting. FINDINGS: Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6-59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7-261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4-92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001). INTERPRETATION: CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile. FUNDING: Turkish Health Institutes Association. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/34246358/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(21)01429-X DB - PRIME DP - Unbound Medicine ER -