A Randomized Phase 2 Study to Evaluate Efficacy and Safety of AR36 for Prevention of Acute Mountain Sickness.

INTRODUCTION: AR36 is a pharmaceutical-grade plant extract used to support cardiovascular health in traditional Chinese medicine. Studies suggest that AR36 may prevent acute mountain sickness (AMS) during gradual ascent to high altitude. This randomized, placebo-controlled Phase 2 trial aimed to evaluate dosing regimens and assess efficacy and safety of AR36 for AMS prevention during rapid ascent. METHODS: Participants received placebo, low-dose AR36 (225 mg twice daily for 14 d prior and 5 d at altitude), or high-dose AR36 (12 d placebo, 300 mg twice daily for 2 d prior and 5 d at altitude). The primary efficacy outcome was 1993 Lake Louise Scoring System (LLSS) score on the morning after ascent. Safety was assessed through the proportion of treatment-emergent adverse events (TEAEs). RESULTS: One hundred thirty-two participants were randomized. Mean±SD age was 31.4±8.6 (range, 19-54) y. Baseline characteristics did not differ across groups. Lake Louise Scoring System scores on Day 16 in the placebo, low-dose, and high-dose groups were 4.03 (2.88), 4.42 (3.17), and 3.5 (2.31), respectively (placebo versus low-dose, P=0.462; placebo versus high-dose, P=0.574; n=110). The incidence of AMS on Day 16 was 66.7% in the placebo, 61.1% in the low-dose, and 55.3% in the high-dose group (P=0.66). The proportion of TEAEs in the placebo, low-dose, and high-dose groups was 38.4% (81), 28.4% (60), and 33.2% (70), respectively (P=0.205; n=127). There was no statistical difference between groups in LLSS, incidence of AMS, or TEAEs. CONCLUSIONS: AR36 did not improve LLSS or AMS incidence using the current regimens. AR36 was well tolerated.

Standards for preclinical research and publications in developmental anaesthetic neurotoxicity: expert opinion statement from the SmartTots preclinical working group.

In March 2019, SmartTots, a public-private partnership between the US Food and Drug Administration and the International Anesthesia Research Society, hosted a meeting attended by research experts, anaesthesia journal editors, and government agency representatives to discuss the continued need for rigorous preclinical research and the importance of establishing reporting standards for the field of anaesthetic perinatal neurotoxicity. This group affirmed the importance of preclinical research in the field, and welcomed novel and mechanistic approaches to answer some of the field's largest questions. The attendees concluded that summarising the benefits and disadvantages of specific model systems, and providing guidance for reporting results, would be helpful for designing new experiments and interpreting results across laboratories. This expert opinion report is a summary of these discussions, and includes a focused review of current animal models and reporting standards for the field of perinatal anaesthetic neurotoxicity. This will serve as a practical guide and road map for novel and rigorous experimental work.