NCT03699839

Brief 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. 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
619

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Oct 2018

Geographic Reach
2 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 5, 2018

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 9, 2018

Completed
17 days until next milestone

Study Start

First participant enrolled

October 26, 2018

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 15, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 15, 2020

Completed
Last Updated

December 17, 2020

Status Verified

December 1, 2020

Enrollment Period

1.8 years

First QC Date

October 5, 2018

Last Update Submit

December 15, 2020

Conditions

InfluenzaOrgan Transplantation

Keywords

VaccinationAdjuvanted vaccineHigh-dose vaccine

Outcome Measures

Primary Outcomes (1)

  • Vaccine response rate

    Seroconversion rate for at least one viral antigen

    day 28 after vaccination

Secondary Outcomes (4)

  • Influenza infection

    Within 6 month after vaccination

  • Seroprotection rates

    At day 28 and month 6 after vaccination

  • Reactogenicity

    within 28 days after vaccination

  • Development of anti-HLA antibodies

    Within 6 months post vaccination

Study Arms (3)

High dose influenza vaccine

EXPERIMENTAL

Administration of high-dose influenza vaccine

Biological: High-dose influenza vaccine

MF59-adjuvanted influenza vaccine

EXPERIMENTAL

Administration of MF59-adjuvanted vaccine

Biological: MF59-adjuvanted influenza vaccine

Standard influenza vaccine

ACTIVE COMPARATOR

Administration of standard intramuscular influenza vaccine

Biological: Standard intramuscular influenza vaccine

Interventions

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.

High dose influenza vaccine
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.

MF59-adjuvanted influenza vaccine
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).

Standard influenza vaccine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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)
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Hospitales Universitarios Virgen del Rocio

Seville, Andalusia, 41013, Spain

Location

Cantonal Hospital Chur

Chur, Kanton Graubünden, 7000, Switzerland

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

University Hospital Bern

Bern, 3010, Switzerland

Location

Hopitaux Universitaires de Genève

Geneva, 1205, Switzerland

Location

CHUV

Lausanne, 1011, Switzerland

Location

Epatocentro Ticino

Lugano, 6900, Switzerland

Location

Canton Hospital St-Gallen

Sankt Gallen, 9007, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Related Publications (6)

  • 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.

    PMID: 20620116RESULT

  • 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.

    PMID: 23465014RESULT

  • 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.

    PMID: 30181045RESULT

  • 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.

    PMID: 26335915RESULT

  • 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.

    PMID: 23546766RESULT

  • 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.

    PMID: 37584344DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsOrthomyxoviridae InfectionsRNA Virus InfectionsVirus DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral VaccinesVaccinesBiological ProductsComplex Mixtures

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

October 5, 2018

First Posted

October 9, 2018

Study Start

October 26, 2018

Primary Completion

August 15, 2020

Study Completion

August 15, 2020

Last Updated

December 17, 2020

Record last verified: 2020-12

Locations

ES(1)CH(8)