PROMPT platform
Background
PROMPT is a multicentre, embedded, multifactorial platform trial designed to efficiently evaluate interventions for preventing perioperative infections and other major postoperative complications. Using a Bayesian adaptive framework, the platform can assess multiple interventions across concurrent or sequential domains and determine whether they are superior, effective, equivalent, inferior, harmful or futile. Interventions may be introduced, modified or discontinued as evidence accumulates, allowing clinically important questions to be answered more rapidly and efficiently than through conventional standalone trials.
PROMPT will enrol adults undergoing a broad range of surgical procedures at more than 60 sites across Australia, New Zealand and international collaborating centres. The primary outcome is the incidence of surgical site infection within 30 days of surgery. Secondary outcomes include other healthcare-associated infections, major postoperative complications, quality of recovery, days alive and at home, and quality of life. The platform initially aims to enrol up to 7800 participants, with capacity to expand as new interventions and research domains are added.
Primary objective
PROMPT aims to rapidly and efficiently identify effective, ineffective or harmful treatments to reduce the incidence of perioperative infections. It will examine the effect of a range of interventions on the incidence of SSI, including superficial, deep and organ-space infections, as defined by the Centers for Disease Control and Prevention (CDC), up to 30 days after surgery. This primary outcome will apply to all domains within the platform unless otherwise specified in a domain-specific appendix (DSA).
Secondary objectives
The secondary objectives include assessing other healthcare-associated infections, such as pneumonia, bloodstream infection and urinary tract infection, using CDC-guided definitions, as well as other major postoperative complications up to 30 days after surgery. Other outcomes include quality of recovery (QoR-15) at three days after surgery, days alive and at home up to 30 days after surgery (DAH30), and quality of life (EQ-5D-5L) at 30 days after surgery. Domain-specific secondary outcomes will be reported in the relevant DSA.
Design
PROMPT is a multicentre, embedded, multifactorial platform trial using a Bayesian adaptive design framework to reach conclusions regarding superiority, efficacy, equivalence, inferiority, harm or futility. PROMPT will be conducted across multiple hospitals in several regions of the world. The specific interventions under investigation will be described in domain-specific appendices.
Population
PROMPT will include participants undergoing a broad range of surgical procedures, including, but not limited to, abdominal, cardiac, orthopaedic, obstetric and gynaecological surgery.
Master inclusion criteria
To be eligible to participate in PROMPT, a patient must meet the following criteria:
- Be an adult patient aged 18 years or older at the time of admission.
- Be scheduled to undergo a surgical procedure involving a skin incision, with an expected duration of at least two hours and a planned overnight hospital stay of at least one night. This includes, but is not limited to, cardiac, orthopaedic, obstetric and gynaecological surgery.
Exclusion criteria
- American Society of Anesthesiologists (ASA) physical status 5: moribund and not expected to survive with or without an operation.
- Poor spoken and/or written language comprehension.
- Previous participation in PROMPT within the preceding 30 days.
Each domain may have additional domain-specific eligibility criteria, typically exclusion criteria, although a combination of inclusion and exclusion criteria may be specified. These criteria are outlined in the relevant DSA. Patients who meet the overall PROMPT eligibility criteria will be assessed for enrolment in all domains active at their site.
The first PROMPT domain to open is the oxygen domain, PROMPT-O2. See the PROMPT-O2 synopsis below for further information.
Progress
PROMPT-O2 has commenced recruitment at Wellington Hospital in New Zealand and Alfred Health in Victoria. Additional sites are progressing through governance processes and are expected to commence recruitment soon.
Trial Steering Committee
Co-chairs
- Professor Paul Myles
- Professor Trisha Peel
Clinical investigators
- Professor Steve Webb
- Professor Wendy Brown
- Professor Tomas Corcoran
- Professor Tracey Bucknall
- Associate Professor Tim Coulson
- Dr Daniel Frei
- Professor Brett Mitchell
Statisticians
- Dr Elizabeth Ryan
- Professor Andrew Forbes
Health economist
- Dr Alisa Higgins
Research managers
- Dianne Mackle – New Zealand
- Australian research manager – to be confirmed
Consumer lead
- Associate Professor Darshini Ayton
Consumer representative
To be confirmed.
Trial sponsor
Monash University
PROMPT-O2
Background
Oxygen is the most commonly used drug during surgery, but the safest and most effective dose remains uncertain. Higher concentrations of oxygen may help the body fight infection and improve wound healing. However, excessive oxygen may also cause harm by contributing to inflammation and organ damage.
Primary objective
PROMPT-O2 is a domain within PROMPT evaluating the effectiveness of three different inspired oxygen concentrations in patients undergoing non-cardiothoracic surgery. The primary outcome is the incidence of SSI.
Secondary objectives
The secondary objectives include assessing other healthcare-associated infections, a pooled composite of serious postoperative complications, and days alive and at home up to 30 days after surgery (DAH30).
Design and intervention
PROMPT-O2 will be conducted as a domain within the PROMPT platform. Patients will be randomly assigned to receive one of the following open-label study interventions:
- Liberal inspired oxygen: FiO2 0.8 (80%).
- Intermediate inspired oxygen: FiO2 0.5 (50%).
- Conservative inspired oxygen: FiO2 ≤0.3 (30%).
Population
Inclusion criteria
As specified in the PROMPT master inclusion criteria above.
Domain-specific exclusion criteria
Patients will be excluded from this domain if they meet any of the following criteria:
- ASA physical status 1 or 2.
- Undergoing cardiac surgery.
- Undergoing thoracic surgery requiring one-lung ventilation.
- Current suspected or confirmed infection.
- Advanced lung disease requiring home oxygen therapy.
- Previous bleomycin therapy.
Known or suspected pregnancy is not an exclusion criterion unless required by the competent national authority within the relevant jurisdiction.
How to get involved
For further information about the study, please contact the interim PROMPT Project Manager.