Effectiveness of Covid-19 Vaccination in Eswatini Against SARS-CoV-2 Associated Hospitalization and Death

NCT04914832 | Completed Phase 4 DMC

• 1 other identifier: Eswatini Implementation & VE
• Study Type: interventional
• Target: 75,012
• Locations: 1 country
• Sites: 1

Brief Summary

Since late December 2019, the novel human coronavirus (SARS-CoV-2) first reported in China, has spread worldwide. Vaccines to prevent SARS-CoV-2 infections have been developed in record time and several candidate vaccines have completed Phase 2a/b and Phase 3 clinical trials. Coronaviruses (CoVs) are spherical, enveloped viruses with positive-sense single-stranded RNA genomes. One fourth of their genome is responsible for coding structural proteins, such as the Spike (S) glycoprotein, envelope, membrane, and nucleocapsid proteins. Envelope, membrane, and nucleocapsid proteins are mainly responsible for virion assembly whilst the S protein is involved in receptor binding, mediating virus entry into host cells during CoVs infection via different receptors. SARS-CoV-2 belongs to the phylogenetic lineage B of the genus Betacoronavirus and it recognizes the ACE2 as the entry receptor. It is the seventh CoV known to cause human infections and the third known to cause severe disease after SARS-CoV and MERS-CoV. AZD1222 is a recombinant replication-defective chimpanzee adenovirus vaccine expressing the SARS-CoV-2 S surface glycoprotein. Development of AZD1222, previously referred to as ChAdOx1 nCoV-19, was initiated by the University of Oxford, UK, with subsequent transfer of development activities to AstraZeneca. The ChAdOx1 platform has been used in 14 clinical studies sponsored by the University of Oxford with immunogens from multiple pathogens such as influenza, tuberculosis, malaria, chikungunya, Zika, MERS-CoV, and Meningitis B. Over 360 healthy adult participants have received ChAdOx1-vectored vaccines in these studies. These vaccines demonstrated robust immunogenicity after a single dose and favourable safety profiles, with no vaccine-related serious adverse events (SAEs).

Conditions

COVID-19; Pneumonia, Viral

Keywords

Vaccine; Effectiveness; COVID-19; pneumonia

Outcome Measures

Primary Outcomes (2)

• Number of HIV-uninfected patients with laboratory-confirmed SARS-CoV-2 illness

  Laboratory-confirmed SARS-CoV-2 illness (COVID-19) hospitalizations and deaths in HIV-uninfected individuals who have been vaccinated with at least 1 dose.

  1 year

• Number of patients with laboratory-confirmed SARS-CoV-2 illness who have been vaccinated with at least one dose

  Laboratory-confirmed COVID-19 hospitalizations and deaths in individuals irrespective of HIV status \[people living with (PLWH) and without HIV\] who have been vaccinated with at least 1 dose.

  1 year

Secondary Outcomes (6)

• Number of HIV-uninfected patients with laboratory-confirmed SAR-CoV-2 illness

  1 year

• Number of patients with laboratory-confirmed SARS-CoV-2 illness who have been fully vaccinated

  1 year

• Number of patients with laboratory-confirmed SARS-CoV-2 illness according to vaccination interval between doses

  1 year

• Number of patients with laboratory-confirmed SARS-CoV-2 illness by genetic variant

  1 year

• Number of patients of special interest with laboratory-confirmed SARS-CoV-2 illness

  1 year

Other Outcomes (3)

• Number of patients with laboratory-confirmed SARS-CoV-2 illness by level of disease severity

  1 year

• Number of days in hospital among patients with laboratory-confirmed SARS-CoV-2 illness

  1 year

• Number of patients with laboratory-confirmed SARS-CoV-2 illness stratified by SARS-CoV-2 seropositivity status

  1 year

Study Arms (1)

All individuals who register on the National Vaccination Registry

EXPERIMENTAL

This will be open-label, single-arm implementation study in Eswatini. All individuals who register on the National Vaccination Registry will be eligible for enrolment. Participants will receive appointments for vaccination using the registry.

Biological: AZD1222

Interventions

AZD1222 BIOLOGICAL

AZD1222 is a recombinant replication-defective chimpanzee adenovirus vaccine expressing the SARS-CoV-2 S surface glycoprotein.

All individuals who register on the National Vaccination Registry

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any individual aged 18 and older eligible to receive AZ1222 vaccine following the national immunization recommendations.
• Willing and able to provide informed consent.

You may not qualify if:

• Any significant acute or chronic medical condition that in the opinion of the vaccinator makes the participant unsuitable for participation in the study or jeopardises the safety of the participant.
• Participant reports being pregnant.
• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine.
• Test negative vaccine effectiveness case-control study
• The study population consists of individuals presenting at the participating hospitals and health centres during the study period, who:
• Either
• Are hospitalized (or died) for an illness consistent with possible COVID-19. Or (in case of other hospital controls)
• Presented to the emergency department (ED) for reasons other than a COVID-19 like illness (e.g. trauma or elective surgery).
• And
• Ever eligible to receive AZ1222 vaccine following the national immunization recommendations prior to hospital admission.
• And
• Willing and able to provide informed consent.
• None

Sponsors & Collaborators

• Shabir Madhi: lead
• AstraZeneca: collaborator

Study Sites (1)

Vaccination Center

Mbabane, Eswatini

Location

Related Publications (7)

• Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, Bellamy D, Bibi S, Bittaye M, Clutterbuck EA, Dold C, Faust SN, Finn A, Flaxman AL, Hallis B, Heath P, Jenkin D, Lazarus R, Makinson R, Minassian AM, Pollock KM, Ramasamy M, Robinson H, Snape M, Tarrant R, Voysey M, Green C, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020 Aug 15;396(10249):467-478. doi: 10.1016/S0140-6736(20)31604-4. Epub 2020 Jul 20.

  PMID: 32702298 BACKGROUND

• Greaney, A. J., A. N. Loes, K. H. D. Crawford, T. N. Starr, K. D. Malone, H. Y. Chu and J. D. Bloom (2021).

  BACKGROUND

• Tegally H, Wilkinson E, Giovanetti M, Iranzadeh A, Fonseca V, Giandhari J, Doolabh D, Pillay S, San EJ, Msomi N, Mlisana K, von Gottberg A, Walaza S, Allam M, Ismail A, Mohale T, Glass AJ, Engelbrecht S, Van Zyl G, Preiser W, Petruccione F, Sigal A, Hardie D, Marais G, Hsiao NY, Korsman S, Davies MA, Tyers L, Mudau I, York D, Maslo C, Goedhals D, Abrahams S, Laguda-Akingba O, Alisoltani-Dehkordi A, Godzik A, Wibmer CK, Sewell BT, Lourenco J, Alcantara LCJ, Kosakovsky Pond SL, Weaver S, Martin D, Lessells RJ, Bhiman JN, Williamson C, de Oliveira T. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature. 2021 Apr;592(7854):438-443. doi: 10.1038/s41586-021-03402-9. Epub 2021 Mar 9.

  PMID: 33690265 BACKGROUND

• Volz, E., S. Mishra, M. Chand, J. C. Barrett, R. Johnson, L. Geidelberg, W. R. Hinsley, D. J. Laydon, G. Dabrera, Á. O'Toole, R. Amato, M. Ragonnet-Cronin, I. Harrison, B. Jackson, C. V. Ariani, O. Boyd, N. J. Loman, J. T. McCrone, S. Gonçalves, D. Jorgensen, R. Myers, V. Hill, D. K. Jackson, K. Gaythorpe, N. Groves, J. Sillitoe, D. P. Kwiatkowski, S. Flaxman, O. Ratmann, S. Bhatt, S. Hopkins, A. Gandy, A. Rambaut and N. M. Ferguson (2021).

  BACKGROUND

• Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Collins AM, Colin-Jones R, Cutland CL, Darton TC, Dheda K, Duncan CJA, Emary KRW, Ewer KJ, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Goodman AL, Green CM, Green CA, Heath PT, Hill C, Hill H, Hirsch I, Hodgson SHC, Izu A, Jackson S, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Lawrie AM, Lelliott A, Libri V, Lillie PJ, Mallory R, Mendes AVA, Milan EP, Minassian AM, McGregor A, Morrison H, Mujadidi YF, Nana A, O'Reilly PJ, Padayachee SD, Pittella A, Plested E, Pollock KM, Ramasamy MN, Rhead S, Schwarzbold AV, Singh N, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Tarrant R, Thomson EC, Torok ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, Watson MEE, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021 Jan 9;397(10269):99-111. doi: 10.1016/S0140-6736(20)32661-1. Epub 2020 Dec 8.

  PMID: 33306989 BACKGROUND

• Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3.

  PMID: 32015507 BACKGROUND

• Fischer, R. J., N. van Doremalen, D. R. Adney, C. K. Yinda, J. R. Port, M. G. Holbrook, J. E. Schulz, B. N. Williamson, T. Thomas, K. Barbian, S. L. Anzick, S. Ricklefs, B. J. Smith, D. Long, C. Martens, G. Saturday, E. de Wit, S. C. Gilbert, T. Lambe and V. J. Munster (2021).

  RESULT

MeSH Terms

Conditions

COVID-19; Pneumonia, Viral; Pneumonia

Interventions

ChAdOx1 nCoV-19

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Vaccines, DNA; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: 1. Open-label, single-arm implementation study. 2. Prospective hospital and mortuary-based case-control study with test-negative controls (test-negative case-control study) and other hospital controls (standard case-control study).

Study Record Dates

• First Submitted: June 1, 2021
• First Posted: June 7, 2021
• Study Start: August 30, 2021
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: August 29, 2023

Record last verified: 2023-08

Locations

ES (1)