Clinical trial NCT02232191: Immunologic Response to Pneumococcal Polysaccharide Vaccine in Splenic Injury Patients
Official title: Immunologic Response to Pneumococcal Polysaccharide Vaccine in Splenic Injury Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Asplenia
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2014-09-05
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Persons without a spleen are susceptible to potentially lethal infections from certain bacteria, with pneumococcus being the most prevalent. Vaccines are provided to help protect against these infections, though they do not so with certainty. Trauma patients who sustain an injury to their spleen currently have three treatment options available for the treating surgeon - nonoperative management, embolization, or removal of the spleen. The purpose of this study is to investigate the antibody response to pneumococcal vaccine in patients undergoing these modes of therapy.

Detailed description: The study is a multi-institutional, prospective trial, conducted primarily at the University of California, Davis Medical Center (UCDMC) by the Department of Surgery, Division of Trauma and Acute Care Surgery. The angioembolization arm will be multicenter while the nonoperative group will be enrolled only at UCDMC. There will be a total of 75 subjects, with 25 in each of the three arms (nonoperative, angioembolization, splenectomy).

Adult trauma patients (defined as those aged 18 to 65 years old) sustaining a splenic injury and planned nonoperative management, are eligible for enrollment in the nonoperative arm. The management decision for the splenic injury is entirely at the discretion of the attending trauma surgeon. Any patient who subsequently undergoes embolization or splenectomy will be withdrawn from the study.

Adult trauma patients sustaining a splenic injury and undergoing splenic artery embolization are eligible for enrollment in this arm of the study. The management decision for the splenic injury is entirely at the discretion of the attending trauma surgeon and radiologist. All patients undergoing successful splenic artery embolization (no subsequent splenectomy or splenorrhaphy, i.e., no cross-over) are eligible.

Patients managed nonoperatively will be vaccinated within three days of their diagnosis, per standard operating protocol at UCDMC. At the time of vaccination, 7cc of venous blood will be collected for baseline antibody analysis. Patients will return four weeks later for a follow-up phlebotomy of another 7cc of blood for analysis of functional antipneumococcal antibody generated in response to vaccine antigen challenge. Blood samples will be centrifuged and stored, and stored sera will be sent in batches on dry ice to Flow Applications, Inc. in McDonough, Georgia for antibody analysis. All samples will be assigned unique patient identifiers.

Responses to the 23-valent pneumococcal polysaccharide vaccine will be measured by ELISA to determine the geometric mean increase in immunoglobulin G (IgG) antibody titer to pneumococcal polysaccharide (Pnc Ps) serotypes. Functional antibody, measured by percent kill of a known pneumococcal concentration, will be determined by opsonophagocytosis assay (OPA). Titers for serogroup 4 and serotypes 6B, 19F, and 23F will be measured, and geometric mean rises in antibody concentrations will be determined to measure response to vaccination.

For those treated with nonoperative management, degree of antibody response and grade of splenic injury will be analyzed against normal controls.

Patients treated via splenic artery embolization will undergo a standard post-embolization computed tomographic exam of the abdomen three to five days postinjury to evaluate the effectiveness of the embolization procedure. The percent of viable, perfused spleen will be calculated from this CT. Antibody response will be compared against the location of the intravascular coils (i.e., proximal versus distal embolization) and the percent of viable spleen as calculated on the follow-up CT scan.

Eligibility criteria: Inclusion Criteria:

* Adult trauma patients (aged 18 to 65 years old) sustaining a splenic injury.

Exclusion Criteria:

* Ages less than 18 and greater than 65
* Initial planned nonoperative management patient who subsequently undergoes embolization or splenectomy will be withdrawn from the study.

Primary outcomes:
measure: Geometric mean increases in pneumococcal antibody titer
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
Study officials:
affiliation: University of California, Davis
name: David Shatz, MD
role: PRINCIPAL_INVESTIGATOR
References: