Browsing by Author "Hanff, Thomas C"

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    ItemOpen Access
    Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.
    (The Lancet. Respiratory medicine, 2021-01-07) Cohen, Jordana B; Hanff, Thomas C; William, Preethi; Sweitzer, Nancy; Rosado-Santander, Nelson R; Medina, Carola; Rodriguez-Mori, Juan E; Renna, Nicolás; Chang, Tara I; Corrales-Medina, Vicente; Andrade-Villanueva, Jaime F; Barbagelata, Alejandro; Cristodulo-Cortez, Roberto; Díaz-Cucho, Omar A; Spaak, Jonas; Alfonso, Carlos E; Valdivia-Vega, Renzo; Villavicencio-Carranza, Mirko; Ayala-García, Ricardo J; Castro-Callirgos, Carlos A; González-Hernández, Luz A; Bernales-Salas, Eduardo F; Coacalla-Guerra, Johanna C; Salinas-Herrera, Cynthia D; Nicolosi, Liliana; Basconcel, Mauro; Byrd, James B; Sharkoski, Tiffany; Bendezú-Huasasquiche, Luis E; Chittams, Jesse; Edmonston, Daniel L; Vasquez, Charles R; Chirinos, Julio A

    Background

    Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.

    Methods

    The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009.

    Findings

    Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m2 (SD 8), and 79 (52%) had diabetes. Compared with discontinuation of renin-angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 [IQR 40-110] for continuation vs 81 [38-117] for discontinuation; β-coefficient 8 [95% CI -13 to 29]). There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ2 test of adverse events between treatment groups p=0·77). There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups.

    Interpretation

    Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19.

    Funding

    REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.
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    ItemOpen Access
    Randomized elimination and prolongation of ACE inhibitors and ARBs in coronavirus 2019 (REPLACE COVID) Trial Protocol.
    (Journal of clinical hypertension (Greenwich, Conn.), 2020-10) Cohen, Jordana B; Hanff, Thomas C; Corrales-Medina, Vicente; William, Preethi; Renna, Nicolas; Rosado-Santander, Nelson R; Rodriguez-Mori, Juan E; Spaak, Jonas; Andrade-Villanueva, Jaime; Chang, Tara I; Barbagelata, Alejandro; Alfonso, Carlos E; Bernales-Salas, Eduardo; Coacalla, Johanna; Castro-Callirgos, Carlos Augusto; Tupayachi-Venero, Karen E; Medina, Carola; Valdivia, Renzo; Villavicencio, Mirko; Vasquez, Charles R; Harhay, Michael O; Chittams, Jesse; Sharkoski, Tiffany; Byrd, James Brian; Edmonston, Daniel L; Sweitzer, Nancy; Chirinos, Julio A
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), is associated with high incidence of multiorgan dysfunction and death. Angiotensin-converting enzyme 2 (ACE2), which facilitates SARS-CoV-2 host cell entry, may be impacted by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), two commonly used antihypertensive classes. In a multicenter, international randomized controlled trial that began enrollment on March 31, 2020, participants are randomized to continuation vs withdrawal of their long-term outpatient ACEI or ARB upon hospitalization with COVID-19. The primary outcome is a hierarchical global rank score incorporating time to death, duration of mechanical ventilation, duration of renal replacement or vasopressor therapy, and multiorgan dysfunction severity. Approval for the study has been obtained from the Institutional Review Board of each participating institution, and all participants will provide informed consent. A data safety monitoring board has been assembled to provide independent oversight of the project.