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Completed

NCT Number: NCT04914832

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

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).

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Key information

Conditions

COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Vaccination Center

Mbabane, Eswatini

About this study

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. Vaccination will be overseen by trained personnel. At enrolment participants will receive an intramuscular injection of AZ1222, a second dose will be given 10 weeks after the first injection. Surveillance for vaccine effectiveness will be performed at designated hospitals.

A prospective hospital-based, case-control study with test-negative controls (test-negative case-control design) and optionally other hospital controls (standard case-control design) will be conducted in parallel with the implementation study. Data will be collected through a network of hospitals located in Eswatini. A hospital-based case control study is an efficient design well suited to study for effectiveness against severe disease, and potentially allows for detailed medical information and additional data collection directly from the patient or healthcare provider. In addition, the study aims to determine the vaccine effectiveness (VE) of AZ1222 against severe disease due to the B.1.351 variant circulating in Southern Africa and other new variants that might evolve.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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

  • Meet the inclusion criteria.

Inclusion criteria

  • Ever eligible to receive AZ1222 vaccine following the national immunization recommendations prior to hospital admission.

And

  • Willing and able to provide informed consent.

Exclusion criteria

  • None

Treatment and study plan

AZD1222

Biological

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

Primary outcomes

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

    Time frame: 1 year

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

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

    Time frame: 1 year

    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.

Secondary outcomes

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

    Time frame: 1 year

    Laboratory-confirmed COVID-19 hospitalizations and deaths in HIV-uninfected individuals who have been fully vaccinated according to the national immunization recommendations.

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

    Time frame: 1 year

    Laboratory-confirmed COVID-19 hospitalizations and deaths in individuals irrespective of HIV status who have been fully vaccinated according to the national immunization recommendations.

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

    Time frame: 1 year

    Laboratory-confirmed COVID-19 hospitalizations and deaths in individuals irrespective of HIV status who have been fully vaccinated according to the vaccine interval in between dose (≤4 weeks, 5-8 weeks, 8-11 weeks, ≥12 weeks).

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

    Time frame: 1 year

    The effect of AZD1222 vaccine on laboratory-confirmed COVID-19 hospitalizations and deaths in individuals irrespective of HIV status who have been vaccinated (with at least 1 dose/ fully vaccinated according to the national recommendations), by viral genetic variants (particularly B.1.351 and non-B.1.351 variants).

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

    Time frame: 1 year

    Laboratory-confirmed COVID-19 hospitalizations and deaths in individuals irrespective of HIV status who have been vaccinated (with at least 1 dose/ fully vaccinated according to the national recommendations), within populations of special interest (e.g. PLWH, specific age groups [special focus on the elderly], Chronic Respiratory Disease, Chronic Cardiovascular Disease, Chronic Kidney Disease, Chronic Liver Disease, Chronic neurologic Disease, Auto-Immune Disease, pregnant women, immunocompromised or specific chronic conditions).

  6. Number of patients with laboratory-confirmed SARS-CoV-2 illness by time since vaccination

    Time frame: 1 year

    The effect of AZD1222 vaccine against laboratory-confirmed COVID-19 hospitalization and death in individuals irrespective of HIV status who have been vaccinated (with at least 1 dose/ fully vaccinated according to the national recommendations), by time since vaccination, including ≤14 days prior to symptom onset.

Other outcomes

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

    Time frame: 1 year

    The AZD1222 vaccine effectiveness against laboratory-confirmed COVID-19 hospitalization and death in individuals irrespective of HIV status who have been vaccinated (with at least 1 dose/ fully vaccinated according to the national recommendations/ fully vaccinated according to the vaccine label), by level of severity. Three mutually exclusive categories: (i) hospital admission without intensive care unit (ICU) admission and without in-hospital death, (ii) ICU admission without in hospital death and (iii) in-hospital death.

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

    Time frame: 1 year

    To estimate the AZD1222 vaccine effect among laboratory-confirmed COVID-19 patients (vaccinated with at least 1 dose/ fully vaccinated according to the national recommendations) on the length of hospital stay (in days).

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

    Time frame: 1 year

    To estimate the AZD1222 vaccine effectiveness against laboratory-confirmed COVID-19 hospitalization and death in individuals irrespective of HIV status who have been vaccinated (with at least 1 dose/ fully vaccinated according to the national recommendations), stratified by SARS-CoV-2 seropositivity status (based on N-protein IgG) at admission.

Sponsors and collaborators

Lead sponsor

Shabir Madhi

Other

Collaborators

  • AstraZeneca

Registry information

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Jun 7, 2021
Registry last updated
Aug 29, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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