Pneumococcal Vaccination to Accelerate Immune Recovery in Sepsis Survivors

Sepsis Clinical Trial

— VACIRiSS  

Official title:

Pneumococcal Vaccination to Accelerate Immune Recovery in Sepsis Survivors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03565159
• Other study ID #: 430321
• Secondary ID: 2017-002236-17
• Status: Completed
• Phase: Phase 4
• Start date: August 2, 2018
• Est. completion date: August 31, 2023

Study information

• Verified date: November 2023
• Source: Guy's and St Thomas' NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 214
• Est. completion date: August 31, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Intervention

Biological:
• Prevenar 13
Pneumococcal polysaccharide conjugate vaccine

Other:
• Sodium Chloride 0.9%
Placebo

Locations

Country	Name	City	State
United Kingdom	Belfast Health and Social Care Trust	Belfast
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	NHS Lothian	Edinburgh
United Kingdom	Royal Surrey County Hospital NHS Foundation Trust	Guildford
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	Manchester University NHS Foundation Trust	Manchester
United Kingdom	Aneurin Bevan University Health Board	Newport
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United Kingdom	Portsmouth Hospitals NHS Trust	Portsmouth
United Kingdom	South Tyneside and Sunderland NHS Foundation Trust	Sunderland

Sponsors (2)

Lead Sponsor	Collaborator
Guy's and St Thomas' NHS Foundation Trust	National Institute for Health Research, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory - Immune recovery patterns	Differences between the intervention and control arms of the following: anti-pneumococcal antibody	Day 0 (baseline) to Day 90
Other	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
Primary	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	Secondary - Precision Estimates	Outcome event data to inform future definitive trial, including: - proportion of rehospitalisation	Up to 365 days
Secondary	Secondary - Precision Estimates	- proportions of reinfections	Up to 365 days
Secondary	Secondary - Precision Estimates	- proportions of reinfection related rehospitalisation	Up to 365 days
Secondary	Secondary - Precision Estimates	- time to first all cause rehospitalisation and	Up to 365 days
Secondary	Secondary - Precision Estimates	- time to first infection requiring antibiotic therapy	Up to 365 days