The Penn Medicine trial is currently enrolling and will evaluate effects across a multitude of outcomes.
A new international trial is aiming to settle the debate surrounding the use of ACE inhibitors (ACEI) and ARBs during the ongoing coronavirus disease 2019 (COVID-19) outbreak.
Launched by investigators from Perelman School of Medicine at the University of Pennsylvania, the REPLACE COVID trial is designed to recruit 152 hospitalized patients already taking medications from the classes and determine whether discontinuing use attenuates or increases the severity of disease symptoms.
“While some data suggests patients with underlying health conditions, like heart disease and high blood pressure, have a higher risk of developing a more severe form of COVID-19, we don’t know whether ACE inhibitors or ARBs are beneficial or harmful,” said co-lead investigator Julio Chirinos, MD, PhD, of associate professor of Cardiovascular Medicine at Perelman School of Medicine, in a statement. “There’s an urgent need to understand how these medications may alter the disease course so we can better guide our treatment for patients who are prescribed these therapies and infected with COVID-19.”
Titled “Elimination or Prolongation of ACE Inhibitors and ARB in Coronavirus Disease 2019 (REPLACECOVID),” the trial, which is currently recruiting, seeks to bring much-needed clarity to the ongoing discussion regarding use of the blood pressure medications. With an estimated completion date of December 31, 2020, the study seeks to randomize consenting patients and assess the impact of temporary discontinuation of ACEI/ARBs on a multitude of outcomes.
Inclusion criteria for the trial include being 18 years of age or older, use of ACEI or ARB as an outpatient prior to admission, and hospitalization with a suspected COVID-19 diagnosis. A dozen exclusion criteria are included in the trial, such as systolic blood pressure less than 100 mmHg or greater than 180 mmHg, eGFR less than mL/min/1.73m2, known pregnancy, and diastolic blood pressure exceeding 110 mmHg.
The primary endpoint of the trial is the development of a global rank score that ranks patient outcomes according to time to death, number of days supported by invasive mechanical ventilation or ECMO, number of days support by renal replacement therapy or pressor/inotropic therapy, and a modified SOFA score. Secondary outcomes included all-cause death, length of hospital stay, area under the curve modified SOFA, and length ICU stay, invasive mechanical ventilation, or ECMO.
“Many people are changing their usual medical management right now based on limited or incomplete information,” said co-lead investigator Jordana Cohen, MD, MSCE, an assistant professor in the division of Renal-Electrolyte and Hypertension at Perelman School of Medicine in the aforementioned statement.
“Until we have high quality evidence, we recommend that patients continue to take these medications as prescribed unless they are told to stop them by their medical provider,” Cohen continued.
Of note, most endpoints will be measured up to 28 days and the trial will be performed on a pragmatic intent-to-treat basis, which allows clinicians the ability change the dose or discontinue the medications if there is a compelling clinical reason.
More information on the trial can be found on the Penn Medicine website.