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InfluenzaPhase 2/3STOP-FLUNCT03699839

Reducing the Burden of Influenza After Solid-Organ Transplantation

A Phase 2/3 study testing High-dose influenza vaccine, MF59-adjuvanted influenza vaccine and Standard intramuscular influenza vaccine in people with Influenza and Organ Transplantation, run by Oriol Manuel at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Influenza is associated with significant morbidity and mortality in solid-organ transplant (SOT) recipients and it is mainly prevented by seasonal influenza vaccination. Unfortunately, the immunogenicity of standard influenza vaccine is suboptimal in this population. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Influenza, Organ Transplantation
What is being tested?
High-dose influenza vaccine, MF59-adjuvanted influenza vaccine and Standard intramuscular influenza vaccine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
619 participants
Where
9 sitesin 2 countries
Study dates
26 Oct 2018to 15 Aug 2020
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of written, informed consent
  • Age ≥18 years
  • Stable outpatients based on clinical judgement
  • ≥ 3 months after solid organ transplantation

Who cannot join

  • Known hypersensitivity to any component (antigen, adjuvant, excipient or preservative) of study vaccines; the composition of the study vaccines is as follows:
  • VaxigripTetra®: hemagglutinin, egg protein, formaldehyde, octylphenol ethoxylate/octoxynol 9 (Triton® X-100), neomycin
  • Fluad®: hemagglutinin, neuraminidase, egg protein, squalene, polysorbate 80, sorbitan trioleate, sodium citrate, citric acid, kanamycin sulphate, neomycin sulphate, barium sulphate, formaldehyde, cetyl trimethylammonium bromide
  • Fluzone-HD®: hemagglutinin, egg protein, formaldehyde, octylphenol ethoxylate/octoxynol 9 (Triton® X-100)
  • Previous life-threatening reaction to influenza vaccine (i.e. Guillain Barré Syndrome)
  • Ongoing therapy for rejection (including steroid pulse or prednisone > 2mg/kg/day over more than 14 days)
Show all 11Show fewer
  • Ongoing therapy with intravenous immunoglobulin (IVIG) and/or eculizumab
  • Current or past (within 6 months) therapy with rituximab
  • Abo incompatible transplantation
  • Unable to comply with study protocol
  • Pregnancy or breastfeeding

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

Switzerland8 sites

  • University Hospital Basel

    Basel, 4031

  • University Hospital Bern

    Bern, 3010

  • Cantonal Hospital Chur

    Chur, Kanton Graubünden, 7000

  • Hopitaux Universitaires de Genève

    Geneva, 1205

  • CHUV

    Lausanne, 1011

  • Epatocentro Ticino

    Lugano, 6900

  • Canton Hospital St-Gallen

    Sankt Gallen, 9007

  • UniversitätsSpital Zürich

    Zurich, 8091

Other trials in Switzerland

Spain1 site

  • Hospitales Universitarios Virgen del Rocio

    Seville, Andalusia, 41013

Other trials in Spain

About this study

Official title: Reducing the Burden of Influenza After Solid-Organ Transplantation: the STOP-FLU Trial [Swiss Trial in Solid Organ Transplantation on Prevention of Influenza]

Influenza is associated with significant morbidity and mortality in solid-organ transplant (SOT) recipients and it is mainly prevented by seasonal influenza vaccination. Unfortunately, the immunogenicity of standard influenza vaccine is suboptimal in this population. Vaccination with a high-dose (HD) influenza vaccine or an MF59-adjuvanted (MF59a) vaccine have significantly reduced the incidence of influenza and increased the immunogenicity of influenza vaccine in the elderly. The investigators will compare the immunogenicity and efficacy of two new vaccination strategies, consisting in vaccination with a HD influenza vaccine or an MF59a influenza vaccine, to the standard-dose non-adjuvanted vaccination (standard of care) in a population of SOT recipients.

Read the detailed description

Objectives: The primary objective of this study is to compare the immunogenicity of two novel vaccination strategies, consisting in vaccination with a HD influenza vaccine or an MF59a influenza vaccine, to the standard-dose non-adjuvanted vaccination (standard of care) in a population of SOT recipients.

The main secondary objectives are to evaluate the efficacy of the novel vaccination strategies in reducing the incidence of influenza, to correlate the humoral responses to vaccination with protection from influenza and to assess the influence of immunosuppression on influenza vaccine responses.

Safety objectives include the assessment of the reactogenicity of the different vaccines and to describe the incidence of acute rejection and the development of anti-Human Leucocyte Antigens (HLA) antibodies after vaccination.

Study design: Prospective double-blinded randomized controlled three-arm parallel group superiority multicenter trial.

Inclusion / Exclusion criteria: Study participants will be enrolled among ≥18-year old stable SOT recipients ≥3 months after transplantation, regularly followed at their respective outpatient clinic at the 7 transplant centers and scheduled to receive the annual influenza vaccine. Candidates will be excluded in case of previous severe reaction or allergy to one of the study vaccines or in case of treatment for acute rejection, among others.

Measurements and procedures: At day 0, after giving informed consent, eligible patients will be randomized in a 1:1:1 ratio into 3 arms: standard quadrivalent intramuscular vaccine (control), HD trivalent vaccine and MF59a trivalent vaccine. After vaccination participants will be followed for a period of 6 months. Safety will be assessed immediately after vaccination and 7, 28 and 180 days after vaccination, and blood sampling for immunogenicity analysis will be performed at baseline, 7, 28 and 180 days after vaccination. Additionally to evaluate the vaccine safety, anti-HLA antibodies will be measured at baseline and at days 28 and 180 after vaccination. Hemagglutinin titers will be determined by hemagglutination inhibition assay (HIA) according to standardized methods. During the influenza season, the development of influenza will be systematically assessed by polymerase chain reaction (PCR) by surveillance nasopharyngeal swab.

Study Product / Intervention: The study intervention consists in the intramuscular administration of either a HD vaccine (containing 60 µg of antigen of each of the three viral strains) [Fluzone-HD®] or a MF59a vaccine (containing 15 µg of antigen of each of the three viral strains with a MF59 adjuvant) [Fluad®].

Control Intervention: The control intervention consists in the administration of the standard quadrivalent non-adjuvanted intramuscular influenza vaccine (VaxigripTetra®), containing 15 µg of each of the four viral strains.

Number of Participants with Rationale: The investigators plan to enroll 780 patients (260 patients per study group). Sample size was calculated to find a significant difference between the three groups for the primary endpoint. The lowest seroconversion rate of 46% for standard dose, a mid seroconversion rate of 59% with MF59a vaccine, and the highest seroconversion rate of 70% with HD vaccine has been assumed. A 10% drop out rate is assumed and the number of patients has been rounded up to get balanced groups. In each group 260 patients are required which amounts to 780 patients.

Being tested
High-dose influenza vaccine, MF59-adjuvanted influenza vaccine, Standard intramuscular influenza vaccine
Keywords
Vaccination, Adjuvanted vaccine, High-dose vaccine
Medical subject headings
Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • High-dose influenza vaccineBiological

    The experimental intervention consists in an intramuscular injection of a MF59-adjuvanted trivalent inactivated influenza vaccine containing 15 µg of antigen per strain (Fluad®) or an intramuscular injection of trivalent inactivated influenza vaccine containing 60 µg of antigen per strain (Fluzone-HD®) and will be performed at day 0.

  • MF59-adjuvanted influenza vaccineBiological

    The experimental intervention consists in an intramuscular injection of a MF59-adjuvanted trivalent inactivated influenza vaccine containing 15 µg of antigen per strain (Fluad®) or an intramuscular injection of trivalent inactivated influenza vaccine containing 60 µg of antigen per strain (Fluzone-HD®) and will be performed at day 0.

  • Standard intramuscular influenza vaccineBiological

    The control intervention consists in an intramuscular injection of one dose of VaxigripTetra®, the standard non-adjuvanted intramuscular influenza vaccine (as routinely done).

Study groups in NCT03699839
Study groupRoleWhat they receive
High dose influenza vaccineExperimentalAdministration of high-dose influenza vaccine
Receives: Biological: High-dose influenza vaccine
MF59-adjuvanted influenza vaccineExperimentalAdministration of MF59-adjuvanted vaccine
Receives: Biological: MF59-adjuvanted influenza vaccine
Standard influenza vaccineActive comparatorAdministration of standard intramuscular influenza vaccine
Receives: Biological: Standard intramuscular influenza vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Vaccine response rate

    Seroconversion rate for at least one viral antigen

    Measured: day 28 after vaccination

Secondary outcomes (4)

  1. Influenza infection

    PCR positive for influenza in a nasopharyngeal swab or other clinical specimen

    Measured: Within 6 month after vaccination

  2. Seroprotection rates

    Antibody levels >40 after vaccination

    Measured: At day 28 and month 6 after vaccination

  3. Reactogenicity

    Self-collected adverse events

    Measured: within 28 days after vaccination

  4. Development of anti-HLA antibodies

    De novo anti-HLA antibodies measured by Luminex

    Measured: Within 6 months post vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2018
  2. Study start26 Oct 2018
  3. Primary completion15 Aug 2020
  4. Study completion15 Aug 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
619 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03699839
Sponsor's protocol ID
2017-01922
Other IDs
2017
Acronym
STOP-FLU
Status last verified
Dec 2020
First submitted
5 Oct 2018
Last updated
17 Dec 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Kumar D, Michaels MG, Morris MI, Green M, Avery RK, Liu C, Danziger-Isakov L, Stosor V, Estabrook M, Gantt S, Marr KA, Martin S, Silveira FP, Razonable RR, Allen UD, Levi ME, Lyon GM, Bell LE, Huprikar S, Patel G, Gregg KS, Pursell K, Helmersen D, Julian KG, Shiley K, Bono B, Dharnidharka VR, Alavi G, Kalpoe JS, Shoham S, Reid GE, Humar A; American Society of Transplantation H1N1 Collaborative Study Group. Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study. Lancet Infect Dis. 2010 Aug;10(8):521-6. doi: 10.1016/S1473-3099(10)70133-X. Epub 2010 Jul 9.

    PubMed 20620116

  • Manuel O, Estabrook M; AST Infectious Diseases Community of Practice. RNA respiratory viruses in solid organ transplantation. Am J Transplant. 2013 Mar;13 Suppl 4(Suppl 4):212-9. doi: 10.1111/ajt.12113. No abstract available.

    PubMed 23465014

  • Mombelli M, Rettby N, Perreau M, Pascual M, Pantaleo G, Manuel O. Immunogenicity and safety of double versus standard dose of the seasonal influenza vaccine in solid-organ transplant recipients: A randomized controlled trial. Vaccine. 2018 Oct 1;36(41):6163-6169. doi: 10.1016/j.vaccine.2018.08.057. Epub 2018 Sep 1.

    PubMed 30181045

  • Kumar D, Campbell P, Hoschler K, Hidalgo L, Al-Dabbagh M, Wilson L, Humar A. Randomized Controlled Trial of Adjuvanted Versus Nonadjuvanted Influenza Vaccine in Kidney Transplant Recipients. Transplantation. 2016 Mar;100(3):662-9. doi: 10.1097/TP.0000000000000861.

    PubMed 26335915

  • Koller MT, van Delden C, Muller NJ, Baumann P, Lovis C, Marti HP, Fehr T, Binet I, De Geest S, Bucher HC, Meylan P, Pascual M, Steiger J. Design and methodology of the Swiss Transplant Cohort Study (STCS): a comprehensive prospective nationwide long-term follow-up cohort. Eur J Epidemiol. 2013 Apr;28(4):347-55. doi: 10.1007/s10654-012-9754-y. Epub 2013 Apr 2.

    PubMed 23546766

  • Mombelli M, Neofytos D, Huynh-Do U, Sanchez-Cespedes J, Stampf S, Golshayan D, Dahdal S, Stirnimann G, Schnyder A, Garzoni C, Venzin RM, Magenta L, Schonenberger M, Walti L, Hirzel C, Munting A, Dickenmann M, Koller M, Aubert JD, Steiger J, Pascual M, Mueller TF, Schuurmans M, Berger C, Binet I, Villard J, Mueller NJ, Egli A, Cordero E, van Delden C, Manuel O. Immunogenicity of High-Dose Versus MF59-Adjuvanted Versus Standard Influenza Vaccine in Solid Organ Transplant Recipients: The Swiss/Spanish Trial in Solid Organ Transplantation on Prevention of Influenza (STOP-FLU Trial). Clin Infect Dis. 2024 Jan 25;78(1):48-56. doi: 10.1093/cid/ciad477.

    PubMed 37584344

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing High-dose influenza vaccine, MF59-adjuvanted influenza vaccine and Standard intramuscular influenza vaccine in people with Influenza and Organ Transplantation, run by Oriol Manuel at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Switzerland, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Vaccine response rate (time frame: day 28 after vaccination). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03699839, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2020; AzTrials last refreshed its copy on 7 Nov 2026.

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