Clinical trial NCT00213265: Safety and Immunogenicity of 7-Valent Pneumococcal Conjugate Vaccine in Children Receiving Solid Organ Transplants
Official title: Safety and Immunogenicity of 7-Valent Pneumococcal Conjugate Vaccine Among Solid Organ Transplant Recipients: Protocol 1A and 1B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Organ Transplant
Immunosuppression
Keywords: organ transplantation
immunosuppression
vaccine
pneumococcal conjugate vaccine
pediatrics
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2005-09-21
Enrollment: 81
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: We plan to study whether the 7-valent pneumococcal conjugate vaccine (Prevnar™) is safe and effective in protecting children who have had a solid organ transplantation and healthy children from pneumococcal infections.

We expect that two or more doses of Prevnar™ will result in similar antibody responses among transplant recipients compared with healthy control subjects, and that children who have undergone solid organ transplant will have a similar number of serious vaccine-related adverse events within 7 days after Prevnar™ as the healthy patients.

Detailed description: Solid organ transplantation (SOT) has emerged as a lifesaving therapy for many patients with end organ failure. SOT recipients have a lifelong increased risk for infections as a result of immunosuppression, including those caused by pneumococci. The increased susceptibility to pneumococcal infections is multi-factorial and is related to underlying immunosuppression as well as varying degrees of splenic dysfunction as a result of underlying pretransplantation diseases, among other factors.

The types and severity of invasive pneumococcal disease vary among each transplant population. However, comparative data are lacking. Lung transplant recipients have the highest incidence of bacterial pneumonia among solid organ transplant recipients. Pneumonia secondary to Streptococcus pneumoniae occurs in heart transplant patients at a rate 10 times that found in the general population. It is suggested that besides the intensity of immunosuppression, ongoing immunosuppression is important as a risk factor for invasive pneumococcal disease in transplant recipients.

Despite the fact that 23-valent polysaccharide pneumococcal vaccine is one of the vaccines that receives priority among organ transplant recipients, at the Hospital for Sick Children, several cases of pneumococcal disease have been seen. The advent of the 7-valent conjugate vaccine affords the opportunity to possibly reduce the burden of pneumococcal disease in the patient population by virtue that it may be more immunogenic in transplant patients

This study will examine the antibody titres achieved among transplant recipients who are immunized with Prevnar™, as well as evaluate the safety and tolerability or Prevnar™ administered as a three-dose regimen to children and adolescents following organ transplantation.

Eligibility criteria: Inclusion Criteria:

Transplant recipients:

* Children 4 months of age up to 18 years of age
* received a kidney, liver, heart, lung or other solid organ transplantation in a Canadian transplant centre
* Informed consent obtained

Healthy Infants and Children:

* Children 2 months to 9 years of age
* no underlying chronic medical conditions
* Informed consent obtained

Exclusion Criteria:

* Previous immunization with pneumococcal vaccine.
* Known hypersensitivity to any of the components of the vaccine, including diphtheria toxoid. Besides the saccharides and CRM197 carrier protein, the vaccine contains aluminum phosphate adjuvant.
* Any significant infection and/or fever at the time of vaccination
* Major acute illness such as clinical instability and acute graft rejection
* Latex allergy

Primary outcomes:
measure: Geometric Mean Concentration of pneumococcal antibodies
timeFrame: Transplant patients: at baseline, just before dose 3, and 6-8 weeks after dose 3; Controls: at baseline, just before dose 3, and 6-8 weeks after dose 3. For those whose series consisted of 1 or 2 doses, at baseline, and 6-8 weeks after doses 1 and 2.
measure: Serious vaccine related adverse events
timeFrame: 7 days post-vaccination
Secondary outcomes:
measure: Nature of immune suppression
timeFrame: 24-28 weeks
measure: Presence of bacterial, viral or other opportunistic infections
timeFrame: 24-28 weeks
measure: Presence of rejection after enrollment
timeFrame: 24-28 weeks
measure: Presence of concurrent diseases or conditions including alterations of renal, hepatic, cardiac and bowel function
timeFrame: 24-28 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children, Toronto Canada
name: Upton Allen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Hospital for Sick Children
name: Upton Allen
role: STUDY_CHAIR
References: