COVIDMED - An early pandemic randomized clinical trial of losartan treatment for hospitalized COVID-19 patients.

Objectives: To assess the efficacy and safety of losartan for COVID-19 patients. Methods: COVIDMED was a double-blinded, placebo-controlled platform RCT. Enrollees were randomized to standard care plus hydroxychloroquine, lopinavir/ritonavir, losartan, or placebo. Hydroxychloroquine and lopinavir/ritonavir arms were discontinued early. We report losartan data vs. combined (lopinavir-ritonavir and placebo) and prespecified placebo-only controls. The primary endpoint was the mean COVID-19 Ordinal Severity Score (COSS) slope of change. Slow enrollment prompted early termination. Results: Fourteen patients were included in our final analysis (losartan [N = 9] vs. control [N = 5] [lopinavir/ritonavir [N = 2], placebo [N = 3]]). Most baseline parameters were balanced. Losartan treatment was not associated with a difference in mean COSS slope of change vs. combined (p = 0.4) or placebo-only control (p = 0.05) (trend favoring placebo). 60-day mortality and overall AE/SAE rates were insignificantly higher with losartan. Conclusion: In this small RCT in hospitalized COVID-19 patients, losartan did not improve outcome and was associated with adverse safety signals.

Avoiding Routine Oxygen Therapy in Patients With Myocardial Infarction Saves Significant Expenditure for the Health Care System-Insights From the Randomized DETO2X-AMI Trial.

Background: Myocardial infarction (MI) occurs frequently and requires considerable health care resources. It is important to ensure that the treatments which are provided are both clinically effective and economically justifiable. Based on recent new evidence, routine oxygen therapy is no longer recommended in MI patients without hypoxemia. By using data from a nationwide randomized clinical trial, we estimated oxygen therapy related cost savings in this important clinical setting. Methods: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized 6,629 patients from 35 hospitals across Sweden to oxygen at 6 L/min for 6-12 h or ambient air. Costs for drug and medical supplies, and labor were calculated per patient, for the whole study population, and for the total annual care episodes for MI in Sweden (N = 16,100) with 10 million inhabitants. Results: Per patient, costs were estimated to 36 USD, summing up to a total cost of 119,832 USD for the whole study population allocated to oxygen treatment. Applied to the annual care episodes for MI in Sweden, costs sum up to between 514,060 and 604,777 USD. In the trial, 62 (2%) patients assigned to oxygen and 254 (8%) patients assigned to ambient air developed hypoxemia. A threshold analysis suggested that up to a cut-off of 624 USD spent for hypoxemia treatment related costs per patient, avoiding routine oxygen therapy remains cost saving. Conclusions: Avoiding routine oxygen therapy in patients with suspected or confirmed MI without hypoxemia at baseline saves significant expenditure for the health care system both with regards to medical and human resources. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01787110.

The Standard of Care Definitions on COVID-19 Pharmacological Clinical Trials: A Systematic Review.

Background: Standard of Care (SoC) has been used with different significance across Randomized Clinical Trials (RCTs) on the treatment of Covid-19. In the context of a living systematic review on pharmacological interventions for COVID-19, we assessed the characteristics of the SoC adopted in the published RCTs. Methods: We performed a systematic review searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to April 10, 2021. We included all RCTs comparing any pharmacological intervention for Covid-19 against any drugs, placebo, or SoC. All trials selected have been classified as studies with SoC including treatments under investigation for COVID-19 (SoC+); studies with SoC without specifications regarding the potential therapies allowed (SoC-); studies including as control groups Placebo (P) or active controls (A+). Results: We included in our analysis 144 RCTs, comprising 78,319 patients. Most of these trials included SoC (108; 75.0%); some in all arms of the study (69.7%) or just as independent comparators (30.3%). Treatments under investigation for COVID-19 in other trials were included in the SoC (SoC+) in 67 cases (62.0%), Thirty-one different therapeutic agents (alone or in combination) were counted within the studies with SoC+: mostly hydroxychloroquine or chloroquine (28), lopinavir/ritonavir (20) or azithromycin (16). No specification was given regarding treatment allowed in the control groups (SoC-) in 41 studies (38.0%). Conclusion: Our analysis shows that the findings emerging from several clinical trials regarding the efficacy and safety of pharmacological intervention for COVID-19 might be jeopardized by the quality of control arms.

Improving racial disparities in unmet palliative care needs among intensive care unit family members with a needs-targeted app intervention: The ICUconnect randomized clinical trial.

INTRODUCTION: The technologies used to treat the millions who receive care in intensive care unit (ICUs) each year have steadily advanced. However, the quality of ICU-based communication has remained suboptimal, particularly concerning for Black patients and their family members. Therefore we developed a mobile app intervention for ICU clinicians and family members called ICUconnect that assists with delivering need-based care. OBJECTIVE: To describe the methods and early experiences of a clustered randomized clinical trial (RCT) being conducted to compare ICUconnect vs. usual care. METHODS AND ANALYSIS: The goal of this two-arm, parallel group clustered RCT is to determine the clinical impact of the ICUconnect intervention in improving outcomes overall and for each racial subgroup on reducing racial disparities in core palliative care outcomes over a 3-month follow up period. ICU attending physicians are randomized to either ICUconnect or usual care, with outcomes obtained from family members of ICU patients. The primary outcome is change in unmet palliative care needs measured by the NEST instrument between baseline and 3 days post-randomization. Secondary outcomes include goal concordance of care and interpersonal processes of care at 3 days post-randomization; length of stay; as well as symptoms of depression, anxiety, and post-traumatic stress disorder at 3 months post-randomization. We will use hierarchical linear models to compare outcomes between the ICUconnect and usual care arms within all participants and assess for differential intervention effects in Blacks and Whites by adding a patient-race interaction term. We hypothesize that both compared to usual care as well as among Blacks compared to Whites, ICUconnect will reduce unmet palliative care needs, psychological distress and healthcare resource utilization while improving goal concordance and interpersonal processes of care. In this manuscript, we also describe steps taken to adapt the ICUconnect intervention to the COVID-19 pandemic healthcare setting. ENROLLMENT STATUS: A total of 36 (90%) of 40 ICU physicians have been randomized and 83 (52%) of 160 patient-family dyads have been enrolled to date. Enrollment will continue until the end of 2021.