Pneumococcal Vaccination to Accelerate Immune Recovery in Sepsis Survivors (VACIRiSS)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Sepsis
• Intervention / Treatment: Biological: Prevenar 13; Other: Sodium Chloride 0.9%

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 214
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom
    • Belfast Health and Social Care Trust
  • Cambridge, United Kingdom, CB2 2QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Edinburgh, United Kingdom, EH16 4SA
    • NHS Lothian
  • Guildford, United Kingdom, GU2 7XX
    • Royal Surrey County Hospital NHS Foundation Trust
  • London, United Kingdom, NW1 2BU
    • University College London Hospitals Nhs Foundation Trust
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust
  • London, United Kingdom, SE1 7EH
    • Guy's and St Thomas' NHS Foundation Trust
  • Manchester, United Kingdom, M13 9WL
    • Manchester University NHS Foundation Trust
  • Newport, United Kingdom, NP20 2EF
    • Aneurin Bevan University Health Board
  • Oxford, United Kingdom, OX3 9DU
    • Oxford University Hospitals NHS Foundation Trust
  • Portsmouth, United Kingdom, PO6 3LY
    • Portsmouth Hospitals NHS Trust
  • Sunderland, United Kingdom, SR4 7TP
    • South Tyneside and Sunderland NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory - Immune recovery patterns	Differences between the intervention and control arms of the following: anti-pneumococcal antibody	Day 0 (baseline) to Day 90
Exploratory - Immune recovery patterns	Differences between the intervention and control arms of the following: B cell subsets, T cell subsets and monocyte HLA-DR and PD-1 expression), function and leukocyte transcriptome	Day 0 (baseline) to Day 90

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborators: National Institute for Health Research, United Kingdom
• Investigators: Principal Investigator: Manu Shankar-Hari, PhD, Guy's and St Thomas' NHS Foundation Trust and King's College London

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2018
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): July 31, 2023

Study Registration Dates

• First Submitted: May 25, 2018
• First Submitted That Met QC Criteria: June 20, 2018
• First Posted (Actual): June 21, 2018

Study Record Updates

• Last Update Posted (Actual): December 14, 2022
• Last Update Submitted That Met QC Criteria: December 12, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 430321; 2017-002236-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: Undecided
• IPD Sharing Access Criteria: Undecided
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No