Tropical Influenza Control Strategies for the Elderly

A Single-centre, Randomised, Observer-blind, Active Comparator-controlled, Superiority Trial of the Immune Response to Six-monthly Versus Annual Standard Dose Inactivated Trivalent Influenza Vaccination in the Elderly

Sponsoren

Hauptsponsor: Tan Tock Seng Hospital

Mitarbeiter: National Healthcare Group, Singapore

Quelle Tan Tock Seng Hospital
Kurze Zusammenfassung

TROPICS1 is a randomized, observer-blind, active comparator-controlled, single-center, Phase IV trial in 200 participants aged ≥65 years. The control group will receive a standard dose licensed trivalent inactivated influenza vaccine at day 1, and an active-comparator (Tetanus-diphtheria-pertussis vaccine) at day 180. Participants in the experimental group will receive the same influenza vaccine at day 1 and day 180. Endpoints are immunological, and include measures of haemagglutination-inhibition (HI) titres, micro-neutralisation titres and cell-mediated immunity at 4 time points after the initial vaccination up to Day 360. The primary hypothesis is that participants receiving an influenza booster at day 180 will achieve superior influenza seroprotection (HI titre ≥1:40) at day 208, compared to controls.

The World Health Organization (WHO) estimates the global annual burden from seasonal influenza as 1 billion infections, with 3-5 million severe cases and 300,000-500,000 deaths. The pattern and impact of these infections varies considerably with climate. In temperate countries, influenza epidemics characteristically occur during the cold winter months, while in sub-tropical countries, they coincide with the rainy seasons. Closer to the equator, influenza virus activity is more complex. In Singapore, biannual epidemics are usual, but with continuous transmission year-round. Bi-annual epidemics, tri-annual epidemics and year round virus activity have also been described in other tropical countries, from Indonesia and Malaysia to Peru and Mexico.

There is no published data reporting year-round influenza vaccine effectiveness in the elderly from countries with continuous influenza virus activity. Despite numerous studies worldwide exploring the HI antibody response to influenza vaccination, the majority of these do not continue follow up beyond seroconversion (21-28 days). However, of the few available, HI antibody titres declined following influenza vaccination in the elderly, such that within 6-12 months geometric mean titres approached pre-vaccination levels. With biannual epidemics and year-round transmission in tropical regions, year-round seroprotection may be important to reduce influenza infections in this environment. A six-monthly vaccination cycle would correspond with the decline in vaccine-induced seroprotection in the elderly, and the 6-monthly periodicity of outbreaks in Singapore and other tropical countries.

Gesamtstatus Completed
Anfangsdatum May 2016
Fertigstellungstermin October 2017
Primäres Abschlussdatum June 2017
Phase Phase 4
Studientyp Interventional
Primärer Ausgang
Messen Zeitfenster
Seroprotection (Proportion of subjects with HI titre ≥1:40 (1/dil) at day 208 post-primary vaccination for each of the influenza strains present in the administered influenza vaccine) Day 208 post-vaccination
Sekundäres Ergebnis
Messen Zeitfenster
Geometric mean titres Day 208 to 360 post-vaccination
Geometric mean ratio Day 208 to 360 post-vaccination
Seroprotection (Proportion of subjects with HI titre ≥1:40 (1/dil) at day 208 post-primary vaccination for each of the influenza strains present in the administered influenza vaccine) Day 360 post-vaccination
Seroconversion (Proportion of subjects achieving seroconversion after vaccination for each of the influenza strains present in the administered influenza vaccine) Day 208 to 360 post-vaccination
Micro-neutralization titres Day 208 to 360 post-vaccination
Influenza-like illness Day 208 to 360 post-vaccination
Influenza infection Day 208 to 360 post-vaccination
Healthcare utilization Day 180 to 360 post-vaccination
Solicited and unsolicited adverse events Day 1 to 7 and day 180 to 187
Serious adverse events Day 1 to 28, and day 180 to 208
Einschreibung 200
Bedingung
Intervention

Interventionsart: Biological

Interventionsname: Influenza vaccine

Beschreibung: Administered at day 1

Interventionsart: Biological

Interventionsname: Influenza vaccine

Beschreibung: Administered at day 180

Armgruppenetikett: Six-monthly influenza vaccine

Interventionsart: Biological

Interventionsname: Tetanus-diphtheria-pertussis vaccine

Beschreibung: Administered at day 180

Armgruppenetikett: Annual influenza vaccine

Teilnahmeberechtigung

Kriterien:

Inclusion Criteria:

1. Age ≥65 years on the day of inclusion

2. No influenza vaccination in the previous 10 months

3. No tetanus, diphtheria or pertussis vaccine in the previous 1 year

4. No virologically confirmed influenza infection in the previous 10 months

5. Able to provide written informed consent

6. Able to attend all scheduled visits and comply with all trial procedures

Exclusion Criteria:

1. Participation in the 4 weeks preceding the first trial vaccination or participation during the present trial period in another trial investigating a vaccine, drug, medical device, or medical procedure

2. History of a life threatening reaction to the vaccine used in the trial, or to a vaccine containing any of the same substances

3. Known systemic hypersensitivity to any of the vaccine components, including:

- Egg protein (eggs or egg products)

- Chicken products

- Formaldehyde

- Neomycin or kanamycin

- Octoxinol 9 (Triton X-100)

- Cetyltrimethylammonium bromide (CTAB)

4. History of Guillain-Barré syndrome (GBS) within 6 weeks following previous influenza vaccination

5. Acute respiratory infection on the day of enrolment

6. Moderate or severe acute illness/infection (according to investigator judgement) on the day of vaccination, or febrile illness (temperature ≥ 37.5°C). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided.

7. Self-reported thrombocytopenia, contraindicating Intramuscular vaccination

8. Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding six months; or long-term systemic corticosteroid therapy (prednisolone ≥ 7.5mg/day or equivalent for more than 2 consecutive weeks within the past 3 months)

9. Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion

10. Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily

11. Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures in the opinion of the Investigator

Geschlecht: All

Mindestalter: 65 Years

Maximales Alter: N/A

Gesunde Freiwillige: Accepts Healthy Volunteers

Insgesamt offiziell
Nachname Rolle Zugehörigkeit
Barnaby Young Principal Investigator Tan Tock Seng Hospital
Ort
Einrichtung: Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital
Standort Länder

Singapore

Überprüfungsdatum

November 2017

Verantwortliche Partei

Art: Sponsor

Schlüsselwörter
Hat den Zugriff erweitert No
Bedingung Durchsuchen
Anzahl der Waffen 2
Armgruppe

Etikette: Six-monthly influenza vaccine

Art: Experimental

Beschreibung: Standard dose trivalent inactivated seasonal influenza vaccine will be administered at day 1 and 180

Etikette: Annual influenza vaccine

Art: Active Comparator

Beschreibung: Standard dose trivalent inactivated seasonal influenza vaccine will be administered at day 1 and an active-comparator (Tetanus-diphtheria-pertussis) at day 180

Akronym TROPICS1
Patientendaten No
Studiendesign Info

Zuweisung: Randomized

Interventionsmodell: Parallel Assignment

Hauptzweck: Prevention

Maskierung: Single (Outcomes Assessor)

Quelle: ClinicalTrials.gov