Real world data on cardiometabolic diseases in U.S. adults during the SARS-CoV-2 pandemic: a decentralized registry study.

BACKGROUND: Pre-existing cardiometabolic comorbidities place SARS-CoV-2 positive patients at a greater risk for poorer clinical course and mortality than those without it. We aimed to analyze real-world registry data focused primarily on participants with cardiometabolic diseases (CMD), which were remotely obtained via a digital platform. METHODS: Participants were divided into two groups: CMD or no cardiometabolic disease (non-CMD). They were evaluated based on their medical history, current medications/supplements, COVID-19 status, demographics, and baseline characteristics. The frequency of medications/supplements for CMD were compared using relative risks and 95% confidence intervals. The WHO (Five) Well-Being Index (WHO-5) were collected monthly for 6 months to assess psychological well-being which included cheerfulness, calmness, vigor, rest, and engagement with daily activities of interest. RESULTS: The 791 enrollees represented 49 U.S. states. The CMD group had significantly higher (p < 0.0001) BMI (mean + 3.04 kg/m2) and age (mean + 9.15 years) compared to non-CMD group. In the CMD group, participants who tested positive for COVID-19 had lower (p < 0.0001) well-being scores than those without COVID-19. For the 274 participants on CMD medications/supplements, there was no statistical difference in risk of COVID-19 contracture based on medication/supplement type; however, all six participants who were not being treated for CMD were COVID-19 positive (RR ~ 104). For 89 participants who were on treatment for diabetes or insulin resistance, there was a 90% reduced risk of COVID-19 incidence (p = 0.0187). CONCLUSION: The well-being score of the CMD group was dependent on whether they tested positive for COVID-19. Type of CMD treatment did not impact COVID-19 status, but absence of treatment significantly increased COVID-19 incidence. With respect to SARS-CoV-2, our analysis supports continued use of the statins, ACE-I, ARBs, and diabetes medications in CMD patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04348942.

Final Results of the RHAPSODY Trial: A Multi-Center, Phase 2 Trial Using a Continual Reassessment Method to Determine the Safety and Tolerability of 3K3A-APC, A Recombinant Variant of Human Activated Protein C, in Combination with Tissue Plasminogen Activator, Mechanical Thrombectomy or both in Moderate to Severe Acute Ischemic Stroke.

OBJECTIVE: Agonism of protease-activated receptor (PAR) 1 by activated protein C (APC) provides neuro- and vasculoprotection in experimental neuroinjury models. The pleiotropic PAR1 agonist, 3K3A-APC, reduces neurological injury and promotes vascular integrity; 3K3A-APC proved safe in human volunteers. We performed a randomized, controlled, blinded trial to determine the maximally tolerated dose (MTD) of 3K3A-APC in ischemic stroke patients. METHODS: The NeuroNEXT trial, RHAPSODY, used a novel continual reassessment method to determine the MTD using tiers of 120, 240, 360, and 540 µg/kg of 3K3A-APC. After intravenous tissue plasminogen activator, intra-arterial mechanical thrombectomy, or both, patients were randomized to 1 of the 4 doses or placebo. Vasculoprotection was assessed as microbleed and intracranial hemorrhage (ICH) rates. RESULTS: Between January 2015 and July 2017, we treated 110 patients. Demographics resembled a typical stroke population. The MTD was the highest-dose 3K3A-APC tested, 540 µg/kg, with an estimated toxicity rate of 7%. There was no difference in prespecified ICH rates. In exploratory analyses, 3K3A-APC reduced ICH rates compared to placebo from 86.5% to 67.4% in the combined treatment arms (p = 0.046) and total hemorrhage volume from an average of 2.1 ± 5.8 ml in placebo to 0.8 ± 2.1 ml in the combined treatment arms (p = 0.066). INTERPRETATION: RHAPSODY is the first trial of a neuroprotectant for acute ischemic stroke in a trial design allowing thrombectomy, thrombolysis, or both. The MTD was 540 µg/kg for the PAR1 active cytoprotectant, 3K3A-APC. A trend toward lower hemorrhage rate in an exploratory analysis requires confirmation. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02222714. ANN NEUROL 2019;85:125-136.