A groundbreaking multicenter clinical trial is underway across Asia to determine optimal antibiotic treatment durations for ventilator-associated pneumonia (VAP), one of the most common and serious hospital-acquired infections in intensive care units.
The REGARD-VAP trial, sponsored by the University of Oxford, is comparing a novel short-course antibiotic strategy against standard-of-care treatment across 31 ICUs in Singapore, Thailand, and Nepal. This hierarchical non-inferiority-superiority trial could fundamentally change how VAP is treated globally.
Clinical Impact and Current Challenges
VAP carries a mortality rate of 20-50% in developed nations and up to 94% in low and middle-income countries. Current diagnostic criteria have limited sensitivity and specificity, often leading to overdiagnosis and excessive broad-spectrum antibiotic use - a key driver of antimicrobial resistance in ICUs.
"The current median treatment duration remains at 12-13 days in Thai academic centers," notes the research team. "This study aims to reduce unnecessary antibiotic use while maintaining effective treatment outcomes."
Novel Treatment Strategy
The trial's intervention arm implements a short-course strategy where antibiotics are discontinued within 7 days if patients meet specific clinical response criteria:
- Temperature normalization for 48 hours
- Stable blood pressure without inotropic support
- For culture-negative cases, antibiotics may be stopped as early as day 3
The control arm follows standard care with minimum 8-day treatment courses, with exact duration determined by treating physicians.
Comprehensive Trial Design
The study employs rigorous methodology including:
- Patient blinding to treatment duration
- Independent blinded expert assessment of pneumonia recurrence
- Stratified randomization by study site
- Regular monitoring of protocol adherence
Primary outcomes measure death and pneumonia recurrence within 60 days post-enrollment. Secondary endpoints include:
- Duration of mechanical ventilation
- Hospital length of stay
- Antibiotic exposure
- Acquisition of multidrug-resistant infections
Scientific Rigor and Safety Monitoring
The trial incorporates multiple safeguards:
- Monthly review of serious adverse events by an independent Data Safety Monitoring Committee
- Four planned interim analyses
- Comprehensive qualitative assessment of implementation challenges
- Collection of respiratory and stool samples for microbiome analysis
With a target enrollment of 460 patients, the trial is powered to detect a non-inferiority margin of 12%. Results could provide definitive evidence for shorter, individualized antibiotic courses in VAP treatment, potentially transforming standard practice while combating antimicrobial resistance.
Regional Significance
The trial's focus on Asian healthcare settings is particularly relevant given the high prevalence of challenging gram-negative pathogens like Pseudomonas aeruginosa and Acinetobacter baumannii in the region. Findings will directly inform treatment protocols where these organisms predominate.
