Browsing by Author "McNulty, Steven E"

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    ItemOpen Access
    Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.
    (JAMA, 2023-07) O'Halloran, Jane A; Ko, Emily R; Anstrom, Kevin J; Kedar, Eyal; McCarthy, Matthew W; Panettieri, Reynold A; Maillo, Martin; Nunez, Patricia Segura; Lachiewicz, Anne M; Gonzalez, Cynthia; Smith, P Brian; de Tai, Sabina Mendivil-Tuchia; Khan, Akram; Lora, Alfredo J Mena; Salathe, Matthias; Capo, Gerardo; Gonzalez, Daniel Rodríguez; Patterson, Thomas F; Palma, Christopher; Ariza, Horacio; Lima, Maria Patelli; Blamoun, John; Nannini, Esteban C; Sprinz, Eduardo; Mykietiuk, Analia; Alicic, Radica; Rauseo, Adriana M; Wolfe, Cameron R; Witting, Britta; Wang, Jennifer P; Parra-Rodriguez, Luis; Der, Tatyana; Willsey, Kate; Wen, Jun; Silverstein, Adam; O'Brien, Sean M; Al-Khalidi, Hussein R; Maldonado, Michael A; Melsheimer, Richard; Ferguson, William G; McNulty, Steven E; Zakroysky, Pearl; Halabi, Susan; Benjamin, Daniel K; Butler, Sandra; Atkinson, Jane C; Adam, Stacey J; Chang, Soju; LaVange, Lisa; Proschan, Michael; Bozzette, Samuel A; Powderly, William G; ACTIV-1 IM Study Group Members

    Importance

    Immune dysregulation contributes to poorer outcomes in COVID-19.

    Objective

    To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

    Design, setting, and participants

    Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021.

    Interventions

    Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day).

    Main outcomes and measures

    The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale.

    Results

    Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies.

    Conclusions and relevance

    Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo.

    Trial registration

    ClinicalTrials.gov Identifier: NCT04593940.
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    ItemOpen Access
    Relief and Recurrence of Congestion During and After Hospitalization for Acute Heart Failure: Insights From Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARESS-HF).
    (Circ Heart Fail, 2015-07) Lala, Anuradha; McNulty, Steven E; Mentz, Robert J; Dunlay, Shannon M; Vader, Justin M; AbouEzzeddine, Omar F; DeVore, Adam D; Khazanie, Prateeti; Redfield, Margaret M; Goldsmith, Steven R; Bart, Bradley A; Anstrom, Kevin J; Felker, G Michael; Hernandez, Adrian F; Stevenson, Lynne W
    BACKGROUND: Congestion is the most frequent cause for hospitalization in acute decompensated heart failure. Although decongestion is a major goal of acute therapy, it is unclear how the clinical components of congestion (eg, peripheral edema, orthopnea) contribute to outcomes after discharge or how well decongestion is maintained. METHODS AND RESULTS: A post hoc analysis was performed of 496 patients enrolled in the Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF) trials during hospitalization with acute decompensated heart failure and clinical congestion. A simple orthodema congestion score was generated based on symptoms of orthopnea (≥2 pillows=2 points, <2 pillows=0 points) and peripheral edema (trace=0 points, moderate=1 point, severe=2 points) at baseline, discharge, and 60-day follow-up. Orthodema scores were classified as absent (score of 0), low-grade (score of 1-2), and high-grade (score of 3-4), and the association with death, rehospitalization, or unscheduled medical visits through 60 days was assessed. At baseline, 65% of patients had high-grade orthodema and 35% had low-grade orthodema. At discharge, 52% patients were free from orthodema at discharge (score=0) and these patients had lower 60-day rates of death, rehospitalization, or unscheduled visits (50%) compared with those with low-grade or high-grade orthodema (52% and 68%, respectively; P=0.038). Of the patients without orthodema at discharge, 27% relapsed to low-grade orthodema and 38% to high-grade orthodema at 60-day follow-up. CONCLUSIONS: Increased severity of congestion by a simple orthodema assessment is associated with increased morbidity and mortality. Despite intent to relieve congestion, current therapy often fails to relieve orthodema during hospitalization or to prevent recurrence after discharge. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00608491, NCT00577135.