Ketamine Low dOse Evaluation on morphine consumption in traumatic patients: study protocol for a randomized, double-blind, placebo-controlled trial (KLOE-Trial)

BACKGROUND: Severely injured trauma patients frequently experience intense acute pain, are highly exposed to opioids during early intensive care, and remain at risk for opioid-related adverse events and persistent pain. Although multimodal analgesia is recommended, regional analgesia may be limited in patients with multiple injuries, coagulopathy, or limited local expertise. Low-dose intravenous ketamine is an attractive opioid-sparing strategy because of its analgesic properties and favourable safety profile at analgesic doses. However, prospective randomized evidence for ketamine used specifically as an analgesic adjunct in critically ill trauma patients remains scarce. METHODS: KLOE is a single-centre, randomized, double-blind, placebo-controlled trial with co-primary objectives of superiority for opioid reduction and non-inferiority for analgesic efficacy. Adult trauma patients with at least two traumatic lesions in two different body regions and at least two regional injuries with an Abbreviated Injury Scale score greater than 1 are randomized 1:1 to receive ketamine or placebo. The intervention consists of ketamine 0.1 mg/kg over 30 min followed by 0.15 mg/kg/h for 48 h; the control group receives volume-matched 0.9% sodium chloride. Study treatment must be started within 12 h after ICU admission. All patients receive protocolized multimodal analgesia. The superiority co-primary endpoint is cumulative opioid consumption at 48 h, expressed as intravenous morphine equivalents. The non-inferiority co-primary endpoint is mean pain intensity over the first 48 h assessed by visual analogue scale, with a non-inferiority margin of 10 mm. The planned sample size was 140 patients. DISCUSSION: This trial will provide prospective randomized evidence on whether early low-dose ketamine infusion can safely reduce opioid exposure in severely injured trauma patients without compromising analgesia. At the time of manuscript submission, recruitment and follow-up have been completed, while data cleaning, blinded data review, database lock, and final statistical analyses are ongoing. Publication of this protocol is intended to ensure transparency of the pre-specified methodology before reporting the main trial results. TRIAL REGISTRATION: ClinicalTrials.gov NCT04833816. First submitted on 5 April 2021; first posted on 6 April 2021. EudraCT 2020-004812-81.