Reducing the Burden of Influenza After Solid-Organ Transplantation
NCT ID: NCT03699839
Last Updated: 2020-12-17
Study Results
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Basic Information
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COMPLETED
PHASE2/PHASE3
619 participants
INTERVENTIONAL
2018-10-26
2020-08-15
Brief Summary
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Detailed Description
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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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
TRIPLE
Study Groups
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High dose influenza vaccine
Administration of high-dose influenza vaccine
High-dose influenza vaccine
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
Administration of MF59-adjuvanted vaccine
MF59-adjuvanted influenza vaccine
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 influenza vaccine
Administration of standard intramuscular influenza vaccine
Standard intramuscular influenza vaccine
The control intervention consists in an intramuscular injection of one dose of VaxigripTetra®, the standard non-adjuvanted intramuscular influenza vaccine (as routinely done).
Interventions
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High-dose influenza vaccine
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
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 vaccine
The control intervention consists in an intramuscular injection of one dose of VaxigripTetra®, the standard non-adjuvanted intramuscular influenza vaccine (as routinely done).
Eligibility Criteria
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Inclusion Criteria
* Age ≥18 years
* Stable outpatients based on clinical judgement
* ≥ 3 months after solid organ transplantation
Exclusion Criteria
* 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
18 Years
ALL
No
Sponsors
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University Hospital, Basel, Switzerland
OTHER
University of Bern
OTHER
University Hospital, Geneva
OTHER
University of Zurich
OTHER
Cantonal Hospital of St. Gallen
OTHER
Fondazione Epatocentro Ticino
OTHER
Cantonal Hospital Chur
UNKNOWN
Hospitales Universitarios Virgen del Rocío
OTHER
Oriol Manuel
OTHER
Responsible Party
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Oriol Manuel
Principal Investigator
Locations
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Hospitales Universitarios Virgen del Rocio
Seville, Andalusia, Spain
Cantonal Hospital Chur
Chur, Kanton Graubünden, Switzerland
University Hospital Basel
Basel, , Switzerland
University Hospital Bern
Bern, , Switzerland
Hopitaux Universitaires de Genève
Geneva, , Switzerland
CHUV
Lausanne, , Switzerland
Epatocentro Ticino
Lugano, , Switzerland
Canton Hospital St-Gallen
Sankt Gallen, , Switzerland
UniversitätsSpital Zürich
Zurich, , Switzerland
Countries
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References
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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.
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.
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.
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.
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.
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.
Other Identifiers
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2017-01922
Identifier Type: -
Identifier Source: org_study_id