Vaccination Response in ImmunoCompromised Host. Immune Response After Vaccination Against Pandemic A/H1N1 Influenza (RICH-3)

This study has been completed.
Sponsor:
Collaborator:
Erasmus Medical Center
Information provided by:
Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT01066169
First received: February 9, 2010
Last updated: January 27, 2012
Last verified: February 2010
  Purpose

As recommended by the Dutch Health Council, certain risk groups and health care workers in The Netherlands were vaccinated to prevent morbidity due to pandemic influenza A/H1N1. Adults were vaccinated twice with the monovalent influenza A/California/2009(H1N1) MF59-adjuvanted surface-antigen vaccine Focetria® (Novartis). The vaccination campaign was executed by general practitioners.

The aim of the study is to verify whether HIV-infected individuals generate an adequate immune response after the first and after the second vaccination.


Condition Intervention
HIV
Biological: Foceteria® (Novartis)

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Immune Response After Vaccination Against Pandemic A/H1N1 Influenza in the Immunocompromised Host. Vaccination Response in ImmunoCompromised Host

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • Antibody titer after second vaccination [ Time Frame: day 55-60 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Antibody titer after second vaccination [ Time Frame: day 17-20 ] [ Designated as safety issue: No ]
  • Antibody titer shortly after first vaccination (day 5-7) [ Time Frame: day 5-7 ] [ Designated as safety issue: No ]
  • HIV replication after vaccination [ Time Frame: day 5-7 ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples Without DNA

Serum, Plasma, Peripheral blood mononuclear cells


Enrollment: 104
Study Start Date: November 2009
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Healthy volunteers
Healthy subjects without HIV, vaccinated with Pandemic Influenza A/H1N1
Biological: Foceteria® (Novartis)
This is not an interventional study. In this observational study we monitored the immune response in a cohort of people who were vaccinated during the national vaccination campaign. The vaccine that was used in The Netherlands is the monovalent influenza A/California/2009(H1N1) MF59-adjuvanted surface-antigen vaccine. It contains 7,5 µg hemagglutinine and the MF59C.1 adjuvant, which is an oil-in-water emulsion, composed of Squalene 9.75 mg, Polysorbate 80 1.175 mg and Sorbitan trioleate 1.175 mg. This vaccine has been approved for use according to a two dose schedule.
HIV-infected patients
HIV-infected patients, vaccinated with Pandemic Influenza A/H1N1
Biological: Foceteria® (Novartis)
This is not an interventional study. In this observational study we monitored the immune response in a cohort of people who were vaccinated during the national vaccination campaign. The vaccine that was used in The Netherlands is the monovalent influenza A/California/2009(H1N1) MF59-adjuvanted surface-antigen vaccine. It contains 7,5 µg hemagglutinine and the MF59C.1 adjuvant, which is an oil-in-water emulsion, composed of Squalene 9.75 mg, Polysorbate 80 1.175 mg and Sorbitan trioleate 1.175 mg. This vaccine has been approved for use according to a two dose schedule.

Detailed Description:

AIM OF THIS STUDY:

Primary objective: Do HIV-infected individuals mount a protective humoral response following vaccination for pandemic influenza A/H1N1 with the monovalent influenza A/California/2009(H1N1) MF59-adjuvanted surface-antigen vaccine Focetria® (Novartis).

Secondary objective: 1) To evaluate the strength of the immune response in HIV-infected individuals compared to healthy volunteers. 2) To evaluate whether a second dose, administered at least 21 days after the first increases the proportion of HIV-infected individuals that have a titer above the threshold associated with protection. 3) To assess whether vaccination is associated with an increases in HIV-replication. 4) To assess whether very early antibody responses occur, which may may indicate immunological memory, for example due to cross reactivity from past influenza infection or vaccination.

STUDY DESIGN:

This is not an interventional study. In this single-centre observational study we will monitor the immune response in a cohort of people who are to be vaccinated during the national vaccination campaign.

Population: The population base for this study consists of HIV-infected adult outpatients at our hospital and of healthy hospital employees. All Dutch and English speaking HIV-infected LUMC outpatients above 18 years of age, on a stable antiretroviral regimen or not yet in need of treatment, are sent a letter inviting them to take part. Healthy hospital employees are invited to take part with a letter, which is handed out upon vaccination. Inclusion is possible until three days after the first vaccination. Exclusion criteria are: use of systemic immunosuppressive medication, an ongoing infection, recent flu-like symptoms and pregnancy. The following characteristics are documented at baseline: age, gender, co-morbidity, medication, year of prior influenza vaccinations and year of diagnosis of HIV infection. All participants are requested to fill out standardized diary assessing flu-like symptoms and use of new medication during the 60 day follow-up.

Laboratory analysis: Lymphocyte counts are determined at baseline, prior to vaccination. A serum sample is taken prior to the first vaccination (day -30 to day 0), prior to the second vaccination (day 17-20) and after the second vaccination (day 60). Viral load is determined at baseline (day -30 to day 0) and after the second vaccination (day 5-7) in a subgroup of 10 persons with undetectable viral load at the preceding outpatient visit. Antibody responses are detected in duplicate for each sample by means of hemagglutination-inhibition (HI) assays according to standard methods at the Erasmus Medical Center in Rotterdam.

Statistical analysis: No formal sample-size calculation was performed. We intend to include a maximum of 100 subjects with HIV and 50 healthy hospital employees. The crude outcome estimates will be adjusted for variables that may influence the outcome (age, CD4 lymphocyte count, use of HAART, viral load).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

HIV patients at the department 'Infectious Diseases' of the Leiden University Medical Centre and healthy volunteers (hospital employees of the Leiden University Medical Centre)

Criteria

Inclusion Criteria:

  • Above 18 years of age
  • Stable antiretroviral regimen or not yet in need of treatment (in case of HIV-infected patients)

Exclusion Criteria:

  • Use of systemic immunosuppressive medication
  • An ongoing infection
  • Recent flu-like symptoms and pregnancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01066169

Locations
Netherlands
Leiden University Medical Centre
Leiden, Zuid-Holland, Netherlands, 2333 ZA
Sponsors and Collaborators
Leiden University Medical Center
Erasmus Medical Center
Investigators
Principal Investigator: Frank P Kroon, MD PhD Leiden University Medical Centre
Study Chair: Leo G Visser, MD PhD Leiden University Medical Centre
Study Chair: Luc BS Gelinck, MD Leiden University Medical Centre
Study Chair: A F Rimmelzwaan, Prof PhD Leiden University Medical Centre
Study Director: Darius Soonawala, MD Leiden University Medical Centre
  More Information

Additional Information:
No publications provided by Leiden University Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: D. Soonawala, MD, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT01066169     History of Changes
Other Study ID Numbers: P09.187
Study First Received: February 9, 2010
Last Updated: January 27, 2012
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Leiden University Medical Center:
Pandemic Influenza A/H1N1
HIV
Antibodies
Replicaton

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 23, 2014