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The Effect of Previous Pneumococcal Immunization on the Immune Response of Patients With Severe CKD to Prevnar 13

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ClinicalTrials.gov Identifier: NCT02370069
Recruitment Status : Completed
First Posted : February 24, 2015
Last Update Posted : September 9, 2021
Sponsor:
Information provided by (Responsible Party):
Marina Ulanova, Lakehead University

Tracking Information
First Submitted Date  ICMJE February 18, 2015
First Posted Date  ICMJE February 24, 2015
Last Update Posted Date September 9, 2021
Actual Study Start Date  ICMJE June 2015
Actual Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 23, 2015)
  • immunogenicity (Fold increase in serotype-specific antibody levels 28 days post-immunization as compared to baseline) [ Time Frame: 0 days, 28 days ]
    Fold increase in serotype-specific antibody levels 28 days post-immunization as compared to baseline
  • immunogenicity (Increase in OPA titres 28 days post-immunization) [ Time Frame: 28 days ]
    Increase in OPA titres 28 days post-immunization
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2015)
  • Longevity of the immune response (Persistence of antibody one year post-immunization) [ Time Frame: 365 days ]
    Persistence of antibody one year post-immunization
  • Longevity of the immune response (Persistence of OPA titres one year post-immunization) [ Time Frame: 365 days ]
    Persistence of OPA titres one year post-immunization
  • Clinical effect (Number of all infectious episodes during one year post-immunization) [ Time Frame: 365 days ]
    Number of all infectious episodes during one year post-immunization
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Previous Pneumococcal Immunization on the Immune Response of Patients With Severe CKD to Prevnar 13
Official Title  ICMJE The Effect of Previous Pneumococcal Immunization on the Immune Response of Adult Patients With Severe Chronic Kidney Disease to Prevnar 13
Brief Summary

Patients with severe chronic kidney disease (CKD) are at a great risk for infection due to their immune system being suppressed. Pneumococcal infection is particularly common and often results in death due to inflammation of lung (pneumonia) or the whole body (sepsis). This infection can be prevented using vaccines which help build protective immunity. The currently recommended pneumococcal vaccine (Pneumovax), however, is often inefficient in this group of patients. There is thus an urgent need to improve the existing vaccination policy.

The goal of this research is to optimize pneumococcal vaccination of patients with severe CKD. Many patients suffering from CKD have already been vaccinated with Pneumovax. Because this vaccine has low immunogenicity in immunocompromised individuals, they may still develop infection. A new vaccine, Prevnar13, has superior immunogenicity and has been recently approved for immunization. There is, however, no specific policy regarding immunization of adult CKD patients, and it is furthermore unknown whether previous Pneumovax immunization negatively affects immune response to Prevnar13.

In order to test whether previous immunization with Pneumovax affects the immune response of severe CKD patients to Prevnar 13, the investigators will immunize two groups of adult stage 4 and 5 CKD patients with one dose of Prevnar 13 and will assess their initial immunological response, its longevity, and vaccine safety. The first group will consist of patients who had been previously immunized with Pneumovax, and the second group will include participants with no history of pneumococcal vaccination.

Antibody levels and opsonophagocytic activity (OPA) will be quantified. The longevity of the immune response will be assessed. As a secondary objective, the immune response will be analyzed in the context of demographic and clinical characteristics of the vaccinated participants.

Detailed Description Adult patients with severe chronic kidney disease (CKD) are immunocompromised and known to have an increased risk of pneumococcal infection. To prevent the infection, immunization with pneumococcal polysaccharide vaccine (PPV23) is currently recommended in Canada; however, the vaccine effect in these patients is suboptimal because of their immune dysfunction. The second-generation pneumococcal vaccines (polysaccharide-protein conjugate) have superior immunogenicity in some immunocompromised adult individuals. In Canada, Prevnar 13 has recently been recommended by the NACI for certain categories of immunocompromised adults, such as HSCT recipients and HIV-positive patients. However, the NACI has concluded that there is currently insufficient evidence to recommend the use of Prevnar 13 in patients with chronic kidney disease. No published data on the use of pneumococcal conjugate vaccines in adults with CKD are available. Moreover, it is unknown whether a previous immunization with PPV23 may have a negative effect on the immune response to Prevnar 13 in these patients. Such a possibility exists due to the memory B-cells' depletion following immunization with pure polysaccharide antigens. In this case, additional doses of Prevnar 13 may be required to achieve the optimal protection. The conjugate vaccine will then expand the B-cell pool available to respond to subsequent antigen challenge. To test whether previous immunization with PPV23 affects the immune response of severe CKD patients to Prevnar 13, we will immunize two groups of adult stage 4 and 5 CKD patients attending the Thunder Bay Regional Health Sciences Centre with one dose of Prevnar 13 and will assess their initial immunological response, its longevity, and vaccine safety. The first group will consist of patients who had been immunized with PPV23 more than one year prior to the enrollment in this study and the second group will include patients without history of pneumococcal vaccination. Fold increase in antibody levels and OPA, as well as longevity of the immune response over a one-year period will be assessed as the surrogate for protection against pneumococcal infection. The immune response will be analyzed in the context of demographic and clinical characteristics of the vaccinated patients. All infectious episodes in the study participants will be recorded throughout one year of observation. We will also record all vaccine adverse effects following immunization and compare their frequency and severity between the two groups. The anticipated results of this trial will provide essential evidence to justify the use of Prevnar 13 for immunization of adult CKD patients.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Chronic Kidney Diseases
Intervention  ICMJE Biological: Prevnar 13
One dose of 0.5 mL Prevnar 13 injected intramuscularly into the deltoid muscle on Day 0.
Study Arms  ICMJE
  • Active Comparator: Previous immunization with PPV23
    Participants who have received a previous vaccination with 1 or more dose of PPV23 at least 12 months previously will receive one dose of 0.5 mL Prevnar 13 study vaccine.
    Intervention: Biological: Prevnar 13
  • Active Comparator: Naive to PPV23
    Participants who have never received a previous vaccination with PPV23 will receive one dose of 0.5 mL Prevnar 13 study vaccine.
    Intervention: Biological: Prevnar 13
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 23, 2015)
138
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2020
Actual Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males and females of 18 years of age or older at the time of the vaccination
  • Severe chronic kidney disease (Stage 4 and 5)

Exclusion Criteria:

  • immunization with PPV23 within the last year
  • any confirmed or suspected immunodeficiency condition, including human immunodeficiency virus (HIV) infection, haematological malignancy, or a congenital immunodeficiency
  • history of allergic disease or reactions likely to be exacerbated by any component of the vaccine
  • history of allergic disease likely to be stimulated by the vaccination
  • history or records of immunosuppressive therapy (with the exception of topical corticosteroids) for more than 14 days and within 6 months of vaccination
  • history or evidence of administration of immunoglobulins and/or any blood products during the study period or within the three months preceding the study vaccine
  • use of any other investigational or non-registered drug or vaccine during the study period or within 30 days preceding the study vaccine
  • administration of a vaccine during the period starting one month before the dose of vaccine and ending one month after
  • pregnancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02370069
Other Study ID Numbers  ICMJE RP-232-08262014
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Marina Ulanova, Lakehead University
Study Sponsor  ICMJE Lakehead University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marina Ulanova, MD, PhD Lakehead University
PRS Account Lakehead University
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP