Bacteremia, Mediastinitis, Staphylococcus Aureus
Conditions
Brief summary
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.
Interventions
BIOLOGICALV710
0.5-mL single injection of V710 (60 µg)
BIOLOGICALPlacebo
0.5-mL single injection of matching placebo
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Staphylococcus Aureus Bacteremia and/or Deep Sternal Wound Infection | Up to 90 days after surgery | 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. |
| Incidence Rate of Vaccine-related Serious Adverse Experiences | Up to 360 days after surgery | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Invasive Staphylococcus Aureus Infection | Up to 90 days after surgery | 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. |
| Number of Participants With Surgical-site Staphylococcus Aureus Infection | Up to 90 days after surgery | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| V710 60 µg V710: 0.5-ml single injection of V710 (60 µg) | 4,005 |
| Placebo Placebo : 0.5-ml single injection of matching placebo | 4,005 |
| Total | 8,010 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 201 | 177 |
| Overall Study | Lost to Follow-up | 144 | 155 |
| Overall Study | Physician Decision | 42 | 48 |
| Overall Study | Progressive disease | 2 | 2 |
| Overall Study | Protocol Violation | 8 | 10 |
| Overall Study | Study terminated by sponsor | 930 | 918 |
| Overall Study | Withdrawal by Subject | 110 | 110 |
Baseline characteristics
| Characteristic | V710 60 µg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 63.6 years STANDARD_DEVIATION 12.6 | 63.9 years STANDARD_DEVIATION 12.5 | 63.8 years STANDARD_DEVIATION 12.5 |
| Sex: Female, Male Female | 1328 Participants | 1336 Participants | 2664 Participants |
| Sex: Female, Male Male | 2677 Participants | 2669 Participants | 5346 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 749 / 3,958 | 343 / 3,967 |
| serious Total, serious adverse events | 291 / 3,958 | 274 / 3,967 |
Outcome results
Primary
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.
Time frame: Up to 360 days after surgery
Population: The population analyzed included all vaccinated participants with follow-up results
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V710 60 µg | Incidence Rate of Vaccine-related Serious Adverse Experiences | 0.0 Events per 100 person-years |
| Placebo | Incidence Rate of Vaccine-related Serious Adverse Experiences | 0.0 Events per 100 person-years |
p-value: 0.99795% CI: [-0.1, 0.1]Miettinen and Nurminen
Primary
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.
Time frame: Up to 90 days after surgery
Population: The population analyzed was the full analysis set: participants who were vaccinated and subsequently underwent cardiothoracic surgery involving full median sternotomy at least 14 days and at most 60 days after vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V710 60 µg | Number of Participants With Staphylococcus Aureus Bacteremia and/or Deep Sternal Wound Infection | 22 participants |
| Placebo | Number of Participants With Staphylococcus Aureus Bacteremia and/or Deep Sternal Wound Infection | 27 participants |
p-value: 0.58495% CI: [-48.6, 55.8]Exact 1-sided binomial test
Secondary
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.
Time frame: Up to 90 days after surgery
Population: The population analyzed was the full analysis set: participants who were vaccinated and subsequently underwent cardiothoracic surgery involving full median sternotomy at least 14 days and at most 60 days after vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V710 60 µg | Number of Participants With Invasive Staphylococcus Aureus Infection | 27 participants |
| Placebo | Number of Participants With Invasive Staphylococcus Aureus Infection | 31 participants |
p-value: 0.34795% CI: [-50.8, 50]Exact 1-sided binomial test
Secondary
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.
Time frame: Up to 90 days after surgery
Population: The population analyzed was the full analysis set: participants who were vaccinated and subsequently underwent cardiothoracic surgery involving full median sternotomy at least 14 days and at most 60 days after vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V710 60 µg | Number of Participants With Surgical-site Staphylococcus Aureus Infection | 53 participants |
| Placebo | Number of Participants With Surgical-site Staphylococcus Aureus Infection | 75 participants |
p-value: 0.03295% CI: [-1.8, 51.2]Exact 1-sided binomial test