Preventing Cardiac Complication of COVID-19 Disease With Early Acute Coronary Syndrome Therapy: A Randomised Controlled Trial. (C-19-ACS)

The outbreak of a novel coronavirus (SARS-CoV-2) and associated COVID-19 disease in late December 2019 has led to a global pandemic. At the time of writing, there have been 150 000 confirmed cases and 3500 deaths. Apart from the morbidity and mortality directly related to COVID-19 cases, society has had to also cope with complex political and economic repercussions of this disease.

At present, and despite pressing need for therapeutic intervention, management of patients with COVID-19 is entirely supportive. Despite the majority of patients experiencing a mild respiratory illness a subgroup, and in particular those with pre-existing cardiovascular disease, will experience severe illness that requires invasive cardiorespiratory support in the intensive care unit.

Furthermore, the severity of COVID-19 disease (as well as the likelihood of progressing to severe disease) appears to be in part driven by direct injury to the cardiovascular system. Analysis of data from two recent studies confirms a significantly higher likelihood of acute cardiac injury in patients who have to be admitted to intensive care for the management of COVID-19 disease.

The exact type of acute of cardiac injury that COVID-19 patients suffer remains unclear. There is however mounting evidence that heart attack like events are responsible. Tests ordinarily performed to definitely assess for heart attacks will not be possible in very sick COVID-19 patients. Randomising patients to cardioprotective medicines will help us understand the role of the cardiovascular system in COVID-19 disease. It will also help us determine if there is more we can do to treat these patients.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Aspirin 75mg; Drug: Clopidogrel 75mg; Drug: Rivaroxaban 2.5 MG; Drug: Atorvastatin 40mg; Drug: Omeprazole 20mg

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Confirmed COVID-19 infection
2. Age =/>40 or diabetes or known coronary disease or hypertension
3. Requires hospital admission for further clinical management.

Exclusion Criteria:

1. Clear evidence of an acute coronary syndrome or myo-pericarditis that requires specific treatment that precludes randomization.
2. Evidence of active bleeding
3. Pregnancy.
4. Age <18 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Arm
Experimental: Active Arm	Drug: Aspirin 75mg; • If patient not on aspirin, add aspirin 75mg once daily unless contraindicated.; Drug: Clopidogrel 75mg; • If patient not on clopidogrel or equivalent, add clopidogrel 75mg once daily unless contraindicated; Drug: Rivaroxaban 2.5 MG; If patient not on an anticoagulation, add rivaroxaban 2.5mg bd unless contraindicated; If patient on DOAC then change to rivaroxaban 2.5mg unless contraindicated; Drug: Atorvastatin 40mg; • If patient not on a statin, add atorvastatin 40mg once daily unless contraindicated; Drug: Omeprazole 20mg; • If patient not on a proton pump inhibitor, add omeprazole 20mg once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	All-cause mortality	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
An ordinal outcome measure of 4 levels (1 - Death, 2 - Intensive Care Unit environment, 3 - In Hospital, 4 - At Home).	- In Hospital, 4 - At Home), using a Bayesian longitudinal ordinal model over 30 days	30 days
Peak troponin	Peak troponin within 7- and 30-days post randomization, if available.	7- and 30- days
Time to discharge	Time to hospital discharge (length of stay)	Up to 30 days
Need for non-invasive ventilatory support	Need for non-invasive ventilatory support, if data available.	30 days
Need for invasive ventilatory support	Need for invasive ventilatory support, if data available.	30 days.
Need for mechanical circulatory support	Need for mechanical circulatory support, if data available.	30 days
Need for renal replacement therapy	Need for renal replacement therapy, if data available.	30 days
Bleeding Academic Research Consortium (BARC) bleed event	Bleeding Academic Research Consortium (BARC) bleed event, adjudicated	30 days
Cessation of randomized active arm therapy	Cessation of randomized active arm therapy	30 days

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Prapa Kanagaratnam, FRCP, PhD, Imperial College Healthcare NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2020
• Primary Completion (Actual): November 30, 2021
• Study Completion (Actual): November 30, 2021

Study Registration Dates

• First Submitted: April 1, 2020
• First Submitted That Met QC Criteria: April 1, 2020
• First Posted (Actual): April 3, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 13, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Coronavirus, SARS-CoV-2, COVID-19, Cardiovascular
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Antimetabolites; Gastrointestinal Agents; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Anti-Ulcer Agents; Proton Pump Inhibitors; Aspirin; Atorvastatin; Clopidogrel; Rivaroxaban; Omeprazole
• Other Study ID Numbers: 20HH5868

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No individual participant data will be shared with other researchers or organisations. Anonymised data might be shared with other research organisations

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No