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van CCT (UK)

van CCT (UK)

Long-term survival and causes of death after influenza vaccination in the elderly.

- candidate number26673
- NTR NumberNTR6179
- ISRCTNISRCTN no longer applicable
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR9-feb-2017
- Secondary IDsMETC 12-4-030 MEC approval Maastricht
- Public TitleLong-term survival and causes of death after influenza vaccination in the elderly.
- Scientific TitleLong-term survival and causes of death after influenza vaccination in the elderly.
- hypothesisInfluenza is a major cause of morbidity and mortality, especially among elderly individuals. Due to ethical constraints, no randomized controlled trials (RCT) are conducted evaluating serious outcomes such as mortality.
Therefore, evidence base consists largely of observational studies that are known to be susceptible to bias. These studies often lead to erroneous estimation of the effectiveness of vaccination and even contradictory results. By adding information on mortality to the data of our previously performed RCT, we aim to counteract some of these methodological limitations and thus examine the influence of vaccination on mortality in an accurate way. We have formulated four main hypotheses we will address in our manuscript:
1) Influenza vaccination of the elderly reduces overall mortality on short-term and long-term.
2) Influenza vaccination of the elderly reduces influenza-related mortality on short-term and long-term.
3) The degree of serologic response to influenza vaccination in vaccinated elderly is positively related to long-term survival.
4) Occurrence of serologically confirmed influenza in unvaccinated elderly is negatively related to long-term survival.
- Healt Condition(s) or Problem(s) studied
- Inclusion criteriaA randomized clinical trial on the efficacy of influenza vaccination in the elderly, involving 31 general practitioners in 15 practices in the southern region of the Netherlands, was conducted in the winter of 1991-1992. All persons aged 60 years or older were invited to enter the trial if they did not belong to those high-risk groups in which vaccination was recommended. At that time, age was no criterion for recommendation. In total 1838 patients (869 male, 989 female) agreed to participate. Of those who enrolled, 490 patients with heart conditions, lung conditions or diabetes mellitus were not considered to belong to the high-risk group by their general practitioner. In order to perform the new study, we complement the data of the previous trial with present information on mortality of the former participants. In specific, date and causes of death are added.

In order to complete our data with additional mortality statistics the Municipal Personal Records Database (Gemeentelijke Basisadministratie, GBA) is searched by a government official to identify the former participants’ “vital status”, i.e. whether they had died, and the date of death if applicable. In case of negative findings we contact the participants’ family practice to enquire about the vital status. If this cannot be provided by the family practice (e.g. due patients’ migration), we request the Netherlands Centre for Family History (Centraal Bureau voor Genealogie, CBG) and – subsequently - an archivist of the Regional Historical Centre of Limburg (Rijksarchief Limburg) to conduct an extensive genealogical search in the national or respectively regional archives. If a search for an individual is not successful, the vital status is checked by the local municipality where the former participant has been living according to our most recent information. Search results of the family practice will be double-checked by the municipalities.

Finally, using the service of Statistics Netherlands (Centraal Bureau voor de Statistiek, CBS) we will verify the dates of death that have been found, and trace back the cause of death of deceased participants up to present time.

The CBS will be asked to perform this search during March 2017.
- Exclusion criteriaAll former trial participants (n=1838) were included. In case of loss to follow-up, the data was censored. No participants were excluded from the analysis.
- mec approval receivedyes
- multicenter trialno
- randomisedyes
- masking/blindingNone
- controlPlacebo
- groupParallel
- Type2 or more arms, randomized
- Studytypeobservational
- planned startdate 1-mrt-2017
- planned closingdate1-sep-2017
- Target number of participants1838
- InterventionsSince this is an observational study on survival of the two groups mentioned below, no other interventions were carried out apart from the vaccine or placebo administration in November 1991.
Previous interventions (RCT 1991/1992):

- intervention group: purified split-virus vaccine containing A/Singapore/6/68(H1N1), A/Beijing/353/89(H3N2), B/Beijing/1/87 and B/Panama/45/90 all with 15 microgram of hemagglutinin, intramuscular injection in deltoid area
- control group: placebo (physiological saline solution), intramuscular injection in deltoid area.

- Primary outcome- overall mortality
- cause-specific mortality
- Secondary outcomeN.A.
- TimepointsOutcome: overall mortality
Timepoints: 1 year, 2 years, 5 years, 10 years, 25 years (after RCT in 1991/1992)

Outcome: cause-specific mortality
Timepoints: 1 year, 2 years, 5 years, 10 years, 25 years (after RCT in 1991/1992)
- Trial web siteN.A.
- statusinclusion stopped: follow-up
- Sponsor/Initiator
- Funding
(Source(s) of Monetary or Material Support)
- PublicationsGovaert TM, Thijs CT, Masurel N, Sprenger MJ, Dinant GJ, Knottnerus JA. The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial. JAMA. 1994 Dec 7;272(21):1661-5.

Cruijff M, Thijs C, Govaert T, Aretz K, Dinant GJ, Knottnerus A. The effect of smoking on influenza, influenza vaccination efficacy and on the antibody response to influenza vaccination. Vaccine. 1999 Feb 5;17(5):426-32

Govaert TM, Sprenger MJ, Dinant GJ, Aretz K, Masurel N, Knottnerus JA. Immune response to influenza vaccination of elderly people. A randomized double-blind placebo-controlled trial. Vaccine. 1994 Oct;12(13):1185-9.

Govaert TM, Dinant GJ, Aretz K, Masurel N, Sprenger MJ, Knottnerus JA. Adverse reactions to influenza vaccine in elderly people: randomised double blind placebo controlled trial. BMJ. 1993 Oct 16;307(6910):988-90.
- Brief summaryWorldwide, only 3 RCT’s on influenza vaccination in community dwelling elderly have been conducted. Among these, we conducted the largest (n=1838) and only randomized double blind trial in the aged, during the 1991-1992 influenza season. This study has shown that in the elderly, influenza vaccination may halve the incidence of serological and clinical influenza.
Now, we set up an observational study based on our randomized trial. In this new study, we explore the effect of influenza vaccination and serologic response to vaccination on short- and long-term survival and cause-specific mortality.
- Main changes (audit trail)
- RECORD9-feb-2017 - 19-feb-2017

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