Exeporfinium chloride (XF-73) nasal gel dosed over 24 hours prior to surgery significantly reduced Staphylococcus aureus nasal carriage in cardiac surgery patients: Safety and efficacy results from a randomized placebo-controlled phase 2 study.

We studied 83 cardiac-surgery patients with nasal S. aureus carriage who received 4 intranasal administrations of XF-73 nasal gel or placebo <24 hours before surgery. One hour before surgery, patients exhibited a S. aureus nasal carriage reduction of 2.5 log10 with XF-73 compared to 0.4 log10 CFU/mL for those who received placebo (95% CI, -2.7 to -1.5; P < .0001).

A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy.

BACKGROUND: This exploratory study was the first study of remimazolam in patients to assess the safety and efficacy of different single doses for procedural sedation. METHODS: Patients scheduled to undergo a diagnostic upper gastrointestinal endoscopy were randomized to receive 1 of 3 doses of remimazolam or midazolam (25 per group) in a double-blind manner. After a single dose of study drug to achieve sedation, patients underwent gastroscopy. We assessed the success of the procedure, sedation levels, recovery from sedation, and safety. RESULTS: A single dose of remimazolam resulted in a successful procedure in 32%, 56%, and 64% of patients in the low (0.10), middle (0.15), and high (0.20 mg/kg) dose groups compared with 44% of patients in the midazolam (0.075 mg/kg) dose group. The onset of sedation was 1.5 to 2.5 minutes in the remimazolam dose groups compared with 5 minutes for midazolam. Because this was a single administration study, sedation could be maintained for as long as necessary to complete the procedure, using rescue midazolam or propofol. Recovery from sedation was rapid for all treatment groups but was influenced by the choice of rescue medication. There were no obvious differences in the safety profiles of remimazolam and midazolam. CONCLUSIONS: This exploratory dose-finding study showed that a single administration of remimazolam (0.10-0.20 mg/kg) was capable of inducing rapid sedation with a quick recovery profile in patients undergoing a diagnostic upper gastrointestinal endoscopy. The safety profile was favorable and appeared to be similar to that of midazolam, warranting further development of this short-acting compound.

A phase Ib, dose-finding study of multiple doses of remimazolam (CNS 7056) in volunteers undergoing colonoscopy.

BACKGROUND: We performed the first multiple dose study of remimazolam designed to assess both the feasibility of maintaining suitable sedation during colonoscopy and reversing the sedative effects of remimazolam with flumazenil. METHODS: Healthy volunteers received fentanyl followed by remimazolam for sedation during colonoscopy. Three dose groups of 15 volunteers each received remimazolam in increasing initial doses, plus top-up doses to maintain sedation for a 30-minute period. In a separate double-blind crossover part of the trial, 6 volunteers were sedated with a single high dose of remimazolam, followed by flumazenil or placebo to reverse the sedation. RESULTS: Successful sedation that was adequate for colonoscopy was achieved in >70% of subjects. After the procedure, subjects rapidly recovered to fully alert, with a median of <10 minutes overall. Failures were due to the inability to sedate or adverse events, with 1 subject failing due to hypotension (arterial blood pressure 80/40) and low SpO2 (<90%). There were no serious adverse events reported, and no events that were unexpected with the combination of a benzodiazepine and fentanyl. The study also showed that sedation was rapidly reversible (1.0 minutes flumazenil vs 10.5 minutes placebo) without resedation. CONCLUSIONS: Remimazolam has the attributes of a sedative drug, with success rates comparable with recent studies of other drugs. Remimazolam provided adequate sedation in 33 of 44 subjects undergoing colonoscopy, and its sedative effects were easily reversed with flumazenil.

A randomised controlled trial on the efficacy and side-effect profile (nausea/vomiting/sedation) of morphine-6-glucuronide versus morphine for post-operative pain relief after major abdominal surgery.

Morphine is the first choice of treatment of severe post-operative pain, despite the occurrence of often discomforting (post-operative nausea or vomiting (PONV)) and sometimes dangerous (sedation, respiratory depression) side effects. Literature data indicate that morphine's active metabolite, morphine-6-glucuronide (M6G), is a powerful analgesic with a possibly more favourable side-effect profile. In this multi-centre randomised controlled clinical trial patients undergoing major abdominal surgery were randomised to M6G or morphine treatment. Treatment started 30-60 min prior to the end of surgery and was continued postoperatively, after patients were titrated to comfort, via patient-controlled analgesia (PCA) for 24-48 h. Pain intensity, nausea, vomiting and sedation scores were collected at regular intervals. In the study 268 patients were randomised to M6G and 249 to morphine. Withdrawal due to insufficient pain relief occurred predominantly just after surgery and was higher in the M6G group (16.8%) than in the morphine group (8.8%), suggesting a slower onset of analgesia for M6G compared to morphine. Subjects who continued on PCA remained equi-analgesic throughout the study. During the first 24h, nausea levels showed a 27% difference in favour of M6G which narrowly failed to reach statistical significance (P=0.052). Sub-analysis showed a significant reduction in nausea levels in females on M6G (30% difference, P=0.034). In all patients, similar reductions of 30-35% were observed in anti-emetic use, vomiting, PONV (a combined measure of nausea and vomiting) in favour of M6G, persisting for the first 24h postoperatively. Reductions in sedation were observed in the first 4h post-operative period for M6G patients.