Pneumococcal Vaccine for Splenic Injury

Overseen By Anthony Calabro, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Davis

Disqualifiers: Age, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of the pneumococcal vaccine (Pneumovax-23) in individuals with spleen injuries. The spleen plays a role in fighting infections, and its absence increases the risk of illness from certain bacteria, such as pneumococcus. The trial will assess the vaccine's efficacy across different treatment groups: those not requiring surgery, those undergoing embolization (a procedure to block blood flow to part of the spleen), and those who have had their spleen removed. Suitable candidates for this trial are adults who have recently sustained a spleen injury and are receiving one of these treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Pneumovax-23, a vaccine for preventing certain infections, is generally safe and well-tolerated. Studies indicate that most people experience only mild side effects, such as pain or swelling at the injection site, fever, or muscle aches. Serious side effects are rare. This vaccine is widely used and recommended, especially for individuals without a spleen, as they are more susceptible to infections. Although limited information exists about using Pneumovax-23 with other vaccines, its overall safety remains reassuring. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Pneumovax-23 vaccine for individuals with splenic injury because it offers a proactive approach to preventing pneumococcal infections, which these patients are particularly vulnerable to. Unlike traditional post-injury or post-splenectomy care that often involves a more reactive strategy, Pneumovax-23 is administered shortly after injury or treatment, either within 72 hours or 14 days post-procedure, depending on the treatment arm. This timing aims to boost the immune response when patients need it most, potentially reducing the risk of severe infections. Additionally, the vaccine's ability to actively stimulate antibody production is a distinctive feature that enhances its protective effect, which is crucial for those undergoing splenic injury management.

What evidence suggests that Pneumovax-23 might be an effective treatment for splenic injury?

Studies have shown that Pneumovax-23 effectively boosts the body's defense against pneumococcal infections. Research indicates that the vaccine is about 42% effective against all types of serious pneumococcal disease and 58% effective against specific types covered by the vaccine. This is especially important for people without a spleen, as they are more prone to these infections. In this trial, participants will receive the Pneumovax-23 vaccine at different times based on their treatment arm: within 72 hours of injury for the Nonoperative arm, 14 days after embolization for the Angioembolization arm, and 14 days after splenectomy for the Splenectomy arm. The vaccine protects them from serious illness and complications related to pneumococcus. Even for those who have had their spleen removed, the vaccine can still trigger a strong immune response, providing significant protection. ^{3 6 7 8 9}

Who Is on the Research Team?

David V Shatz, MD

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for adult trauma patients aged 18 to 65 who have sustained a splenic injury. It's not open to those under 18 or over 65, and if someone initially managed without surgery needs embolization or spleen removal later, they'll be taken out of the study.

Inclusion Criteria

I am between 18 and 65 years old and have a spleen injury from an accident.

Exclusion Criteria

I was initially not planned for surgery but had to undergo embolization or splenectomy and will be withdrawn from the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive the pneumococcal vaccine and baseline antibody levels are drawn

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for antibody response to the vaccine

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Pneumovax-23

Trial Overview The study is examining how well patients with splenic injuries respond to the Pneumovax-23 vaccine. This response will be compared across three different treatments: nonoperative management, embolization, and spleen removal.

How Is the Trial Designed?

Group I: Nonoperative Active Control 1 Intervention

Pneumococcal vaccine (Pneumovax-23) will be administered within 72 hours of injury. Baseline antibody levels will be drawn at the time of vaccine administration, with response levels being drawn 4 weeks later.

Group II: Angioembolization Active Control 1 Intervention

Pneumococcal vaccine (Pneumovax-23) will be administered 14 days after embolization. Baseline antibody levels will be drawn at the time of vaccine administration, with response levels being drawn 4 weeks later.

Group III: Splenectomy Active Control 1 Intervention

Pneumococcal vaccine (Pneumovax-23) will be administered 14 days after splenectomy. Baseline antibody levels will be drawn at the time of vaccine administration, with response levels being drawn 4 weeks later.

Pneumovax-23 is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Pneumovax 23 for:

• Prevention of pneumococcal disease caused by the 23 serotypes of Streptococcus pneumoniae

Approved in European Union as Pneumovax 23 for:

• Prevention of pneumococcal disease caused by the 23 serotypes of Streptococcus pneumoniae

Approved in Canada as Pneumovax 23 for:

• Prevention of pneumococcal disease caused by the 23 serotypes of Streptococcus pneumoniae

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Published Research Related to This Trial

In a study of 43 critically ill patients (16 burn and 27 neurosurgical), 87.5% of burn patients generated a successful immunologic response to the PPSV23 vaccine, compared to only 40.7% of neurosurgical patients, indicating that burn injury enhances vaccine responsiveness.

Burn patients not only had a higher rate of successful responses but also showed significantly greater median antibody levels and fold rises in IgG concentrations post-vaccination, suggesting that the type of injury influences the effectiveness of the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Divergent humoral responses to 23-valent pneumococcal polysaccharide vaccine in critically-ill burn and neurosurgical patients. Mueller, SW., Baumgartner, LJ., MacLaren, R., et al.[2018]

Pneumococcal vaccines, including the 23-valent polysaccharide vaccine (PPSV23) and the 13-valent conjugate vaccine (PCV13), have significantly reduced infections caused by Streptococcus pneumoniae in both children and adults, highlighting their efficacy in preventing serious diseases like pneumonia and meningitis.

The development of new vaccine candidates is crucial due to observed serotype replacement with virulent strains not covered by existing vaccines, with eight potential protein antigens currently being researched for future pneumococcal vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens. Daniels, CC., Rogers, PD., Shelton, CM.[2020]

In a study of 4128 elderly outpatients with chronic respiratory diseases, the 23-valent pneumococcal polysaccharide vaccine (PPSV23) was associated with a significantly lower risk of pneumococcal pneumonia, with an adjusted odds ratio of 0.39.

The vaccine showed even greater effectiveness in older age groups, with adjusted odds ratios of 0.16 for those aged 70 and 0.15 for those aged 75 and older, indicating strong protective benefits for the elderly population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of a 23-valent pneumococcal polysaccharide vaccine for the prevention of pneumococcal pneumonia in the elderly with chronic respiratory diseases: a case-control study of a single center. Masuda, T., Nakatani, E., Shirai, T., et al.[2021]

The new pneumococcal conjugate vaccines, PCV15 and PCV20, have been shown to be safe and immunogenic in adults, providing a promising alternative to the previously recommended PCV13 and PPSV23 vaccines.

PCV13 demonstrated efficacy rates of 75% against PCV13-type invasive pneumococcal disease (IPD) and 45% against pneumococcal pneumonia (PP), while PPSV23 showed lower effectiveness of 45% against PPSV23-type IPD and only 18% against PPSV23-type PP, indicating that PCV13 offers better protection in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review and Meta-Analysis of the Efficacy and Effectiveness of Pneumococcal Vaccines in Adults. Farrar, JL., Childs, L., Ouattara, M., et al.[2023]

A quality improvement initiative successfully increased the PPSV23 vaccination rates for high-risk pediatric patients from approximately 20% to 60% over a 12-month period across three specialty clinics.

The project involved implementing automated pre-visit planning reports and stocking vaccines, demonstrating that organized strategies can significantly enhance vaccination rates in vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving Pneumococcal Vaccination Rates in High-risk Children in Specialty Clinics. Harris, JG., Harris, LA., Olarte, L., et al.[2022]

In a study of 46 kidney transplant recipients, sequential vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by the pneumococcal polysaccharide vaccine (PPSV23) resulted in significantly higher anti-pneumococcal antibody levels compared to baseline, indicating effective immune response.

No patients developed pneumococcal-associated pneumonia or experienced vaccination-related allograft rejection during the 12-month follow-up, suggesting that this vaccination strategy is both safe and effective for kidney transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody responses after sequential vaccination with PCV13 and PPSV23 in kidney transplant recipients. Mülling, N., van de Sand, L., Völk, K., et al.[2023]

In a study of 96 patients with chronic pulmonary diseases, the 23-valent polysaccharide pneumococcal vaccine (PPV-23) did not significantly reduce the overall risk of pneumococcal pneumonia, suggesting limited effectiveness in this high-risk group.

While there was a trend indicating potential benefits of vaccination against bacteremic pneumonia in older patients (75 years and older), the results were not statistically significant, highlighting the uncertainty surrounding the vaccine's efficacy in preventing pneumonia among patients with chronic pulmonary conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia in patients with chronic pulmonary diseases: a matched case-control study. Vila-Corcoles, A., Ochoa-Gondar, O., Rodriguez-Blanco, T., et al.[2014]

In a study involving 10 adults (5 young and 5 old), the PCV13 vaccine successfully induced CD4 T-cell responses in all participants, with older individuals showing stronger and more polyfunctional responses compared to younger ones.

The presence of T follicular helper (Tfh) cells in younger participants correlated with improved antibody responses after receiving the PPSV23 booster, highlighting the role of Tfh cells in enhancing vaccine efficacy against pneumococcal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral CD4 T follicular cells induced by a conjugated pneumococcal vaccine correlate with enhanced opsonophagocytic antibody responses in younger individuals. Sterrett, S., Peng, BJ., Burton, RL., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC98850/

Pneumococcal Conjugate Vaccines Overcome Splenic ... We show that in rats, vaccination with a pneumococcal conjugate vaccine can induce good antibody responses even after splenectomy, particularly after a second ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9593971/

Effectiveness of the 23-valent pneumococcal ... The adjusted vaccine effectiveness was 42% (95% confidence interval (CI): 9–63%) for all-serotype IPD and 58% (95% CI: 21–78%) for PPV23- ...

3. mdpi.com mdpi.com/2218-273X/10/5/704

Autologous Splenocyte Reinfusion Improves Antibody ... We found that splenectomy impaired the immune response in the splenectomized group compared to the non-splenectomized group; the splenectomized group with ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02232191

Study Details | NCT02232191 | Immunologic Response to ... Pneumococcal vaccine (Pneumovax-23) will be administered 14 days after splenectomy. Baseline antibody levels will be drawn at the time of vaccine administration ...

5. thelancet.com thelancet.com/journals/lanrhe/article/PIIS2665-9913(24)00128-0/fulltext

Effectiveness of pneumococcal vaccination in adults with ... Our study found that pneumococcal vaccination was protective against morbidity and mortality due to pneumonia among patients with common immune- ...

6. fda.gov fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert-PNEUMOVAX-23_0.pdf

Package Insert - PNEUMOVAX 23 Limited safety and immunogenicity data from clinical trials are available on the concurrent administration of PNEUMOVAX 23 and vaccines other than ZOSTAVAX.

7. cdc.gov cdc.gov/pneumococcal/hcp/vaccine-recommendations/risk-indications.html

Summary of Risk-based Pneumococcal Vaccination ... Give 1 dose of PCV20 or PPSV23 at least 8 weeks after the last PCV dose. · When PCV20 is used, their pneumococcal vaccinations are then complete.

8. rxlist.com rxlist.com/pneumovax-23-drug.htm

Pneumovax 23 (Pneumococcal Vaccine Polyvalent) Limited safety and immunogenicity data from clinical trials are available on the concurrent administration of PNEUMOVAX 23 and vaccines other than ZOSTAVAX.

9. pdf.hres.ca pdf.hres.ca/dpd_pm/00072367.PDF

pneumovax® 23 The highest risk group includes persons with functional or anatomic asplenia (e.g., sickle cell disease or splenectomy), HIV infection, leukemia ...