Efficacy, Immunogenicity, and Safety of a Single Dose of V710 in Adult Patients Scheduled for Cardiothoracic Surgery (V710-003 AM2)

Study Overview
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Brief Summary
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This study will assess the efficacy of a single dose of V710 vaccine to prevent serious Staphylococcus aureus infections following elective cardiothoracic surgery. The study will also evaluate the immune response and general safety of the V710 vaccine.

Official Title
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A Randomized, Multicenter, Double-Blind, Group-Sequential Study to Evaluate the Efficacy, Immunogenicity, and Safety of a Single Dose of Merck 0657nI Staphylococcus Aureus Vaccine (V710) in Adult Patients Scheduled for Cardiothoracic Surgery

Conditions
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Staphylococcus Aureus, Bacteremia, Mediastinitis

Intervention / Treatment
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* Biological: V710
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is scheduled to undergo cardiothoracic surgery involving a full median sternotomy (not including cardiac transplantation surgery) within 14 to 60 days after vaccination. Female participants of reproductive potential are required to have a negative urine or serum pregnancy test immediately prior to study vaccination and must use an acceptable form of birth control. Exclusion Criteria: Participants had an invasive Staphylococcus aureus infection within the past 3 months prior to study entry. A realistic (>50%) possibility that cardiothoracic surgery will be necessary sooner than 10 days after vaccination. Participant is planning to undergo cardiac transplantation surgery or sternal debridement to remedy an infection resulting from a prior cardiothoracic surgery. Participant has any type of ventricular-assist device in place at the time of study entry. Participant has a history of anaphylaxis to any of the vaccine components. Participant received V710 vaccine, any other investigational Staphylococcus aureus vaccine, or investigational Staphylococcus aureus antibodies. Participant has a temperature of ≥100.4ºF (≥38.0ºC), oral equivalent, within 48 hours prior to study vaccination. Participant has impairment of the immune system. Participant has a medical condition in which the expected survival is less than 90 days.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V710 60 µg<br> | Biological: V710<br>* 0.5-mL single injection of V710 (60 µg)<br>* Other names: Merck 0657nI Staphylococcus aureus vaccine;|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* 0.5-mL single injection of matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Staphylococcus Aureus Bacteremia and/or Deep Sternal Wound Infection | Diagnosis of the Staphylococcus aureus infections employed standardized definitions adapted from the Centers for Disease Control (CDC) Guidelines for Nosocomial infections (Garner JS, Jarvis WS, Emori TG, et al. CDC definitions for nosocomial infections. APIC Infect Control App Epidemiol 1996;A1-20). Bacteremia was defined as ≥1 positive blood culture for S. aureus regardless of the presence of clinical symptoms. A Staphylococcus aureus deep sternal wound infection included mediastinitis or a deep incisional surgical-site infection involving the sternal wound. | Up to 90 days after surgery | 
| Incidence Rate of Vaccine-related Serious Adverse Experiences | Vaccine-related adverse experiences were those deemed by the investigator to be possibly, probably, or definitely vaccine related. A serious adverse experience was any adverse experience occurring at any dose that 1) resulted in death, 2) was life threatening, 3) resulted in a persistent or significant disability/incapacity, 4) resulted in or prolonged an existing inpatient hospitalization, 5) was a congenital anomaly/birth defect, 6) was a cancer, 7) was an overdose, or 8) jeopardized the participant and required medical or surgical intervention. | Up to 360 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Invasive Staphylococcus Aureus Infection | Diagnosis of the Staphylococcus aureus infections employed standardized definitions adapted from the CDC Guidelines for Nosocomial infections. An invasive Staphylococcus infection included bacteremia, deep sternal wound infection, deep-tissue organ/space infection at another surgical site, or any other deep-tissue infection. | Up to 90 days after surgery | 
| Number of Participants With Surgical-site Staphylococcus Aureus Infection | Diagnosis of the Staphylococcus aureus infections employed standardized definitions adapted from the CDC Guidelines for Nosocomial infections. A Staphylococcus infection surgical-site infection included any superficial incisional, deep incisional, or organ/space infection at the sternal site, the vascular harvest (donor) site, or any other site at which the surgery was performed. | Up to 90 days after surgery |