Pneumococcal Vaccination to Accelerate Immune Recovery in Sepsis Survivors

Study Overview
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Brief Summary
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The VACIRiSS trial is a phase-IV, multi-centre placebo controlled randomised trial of conjugate pneumococcal vaccine in adult sepsis survivors.

Detailed Description
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The aim of VACIRiSS trial is to evaluate the immunogenicity and heterologous effects of single dose 13-valent conjugate pneumococcal vaccine (PCV-13) in preventing infection related rehospitalisation in sepsis survivors and to collect outcome event data with necessary precision to inform future definitive trial design.

Official Title
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Pneumococcal Vaccination to Accelerate Immune Recovery in Sepsis Survivors

Conditions
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Sepsis

Intervention / Treatment
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* Biological: Prevenar 13
* Other: Sodium Chloride 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who meet all the following inclusion criteria are eligible to participate in the trial. Male or female adult patients aged 18 years or older on the date of screening for the trial Registered with a General Practitioner Reason for admission to intensive care unit or high dependence unit (HDU) was sepsis Clinical condition has improved and the patient is ready for step down to HDU or ward based care in the next 24 - 48 hours Provision of written informed consent by the patient OR by patient's Legal Representative OR Professional Consultee. Exclusion Criteria: Patients who meet one or more of the following will be excluded from the trial. Core temperature ≥38.0°C within the past 24 hours prior to study IMP administration. As with other vaccines, the administration of Prevenar 13 should be postponed in subjects suffering from acute, severe febrile illness. However, the presence of a minor infection, such as a cold, should not result in the deferral of vaccination. Hypersensitivity reaction (e.g., anaphylaxis) to any component of Prevenar 13 or any diphtheria toxoid-containing vaccine. Recent vaccination defined as any vaccination administered to subjects within 7 days of enrolment. Pregnant and lactating women. Limitations of care set including not for resuscitation, not for readmission to critical care. Residence in a nursing home, long-term care facility, or other institution, or requirement of semiskilled nursing care. (An ambulatory subject who was a resident of a retirement home or village is eligible for the trial.) As the IMP is administered intra muscularly, coagulopathy defined as platelet count less than 50 x 109/L and/or International Normalized Ratio (INR) greater than 1.3. For this exclusion criteria bloods taken within 72 hours of screening are valid. If these standard of care blood results are not available, then these should form part of the screening bloods for assessing eligibility. Splenectomy (previous or in the current admission) Diagnosis of pneumococcal sepsis in the current admission APACHE II score defined Immune deficiency or suppression, defined as presence of 1 or more of the following conditions: Documented human immunodeficiency virus (HIV) infection at any time-point pre-trial. If previous results are not available and/or current admission is not due to HIV infection, these patients do not need new testing and are considered eligible for the trial. leukaemia (presence defined as having been treated by or been eligible for treatment by radiotherapy and/or chemotherapy within the last 5 years) lymphoma (presence defined as having been treated by or been eligible for treatment by radiotherapy and/or chemotherapy within the last 5 years) Hodgkin disease (presence defined as having been treated by or been eligible for treatment by radiotherapy and/or chemotherapy within the last 5 years) multiple myeloma (presence defined as having been treated by or been eligible for treatment by radiotherapy and/or chemotherapy within the last 5 years) malignancy (defined as presence of any malignancy that had been treated by or had been eligible for treatment by radiotherapy and/or chemotherapy within the last 5 years) chronic renal failure (defined as receipt of renal dialysis or transplant) or nephrotic syndrome receipt of immunosuppressive therapy, including steroids, within 3 months of study vaccine administration (For corticosteroids, prednisone or equivalent 0.5 mg/kg/day for 14 days or longer. Inhaled, intra- articular, and topical steroids are not considered immunosuppressive). Receipt of an organ or bone marrow transplant with ongoing immunosuppressive medications. Failed previous transplant patients not currently on immunosuppression are eligible.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomised 1:1 to receive one single 0.5ml dose of active or placebo Investigational Medicinal Product at baseline.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prevenar 13<br>A volume of 0.5ml will be drawn up into a syringe and labelled with an Annex 13 label. | Biological: Prevenar 13<br>* Pneumococcal polysaccharide conjugate vaccine<br>|
| Placebo Comparator: Sodium chloride 0.9%<br>A volume of 0.5ml will be drawn up into a syringe and labelled with an Annex 13 label. | Other: Sodium Chloride 0.9%<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary - Time to Event | Comparison of the time taken for infection related rehospitalisation or death between intervention and control arms. | Up to 365 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary - Precision Estimates | Outcome event data to inform future definitive trial, including: - proportion of rehospitalisation | Up to 365 days | 
| Secondary - Precision Estimates | - proportions of reinfections | Up to 365 days | 
| Secondary - Precision Estimates | - proportions of reinfection related rehospitalisation | Up to 365 days | 
| Secondary - Precision Estimates | - time to first all cause rehospitalisation and | Up to 365 days | 
| Secondary - Precision Estimates | - time to first infection requiring antibiotic therapy | Up to 365 days |