Managing Endothelial Dysfunction in COVID-19 : A Randomized Controlled Trial at LAUMC

• Status: Recruiting
• Trial end date: 2021-06-01
• Target enrollment: 0
• Participant gender: All

Summary

COVID-19 infection was shown to cause endothelial dysfunction .

At the level of the endothelium the pathophysiological mechanisms have been hypothesized and were divided into pro-coagulant, pro-inflammatory, anti-fibrinolytics, impaired barrier function, vasoconstrictor and pro-oxidant. So far, the pro-coagulant and pro-inflammatory pathways have been studied and as a result dexamethasone and anticoagulation became part of the standard therapies for the disease. However, so far, no RCT has been evaluated on targeting the vasoconstrictive and antioxidant pathways with an aim of revealing clinical benefit.

So, with this trial we intend to provide a regiment composed of several medications we hypothesize will act on several downstream pathways that would improve endothelial function primarily via the increase in NO production and release.

At the time of this proposal there has been no randomized trials evaluating or testing the use of cardiovascular drugs targeting endothelial dysfunction in COVID-19 patients. As previously noted there has been a call to study these drugs and their effect after a strong research regarding their theorized effectiveness. For evidence, there was a recently published meta-analysis evaluating the role of statins in COVID-19 with preliminary findings suggested a reduction in fatal or severe disease by 30% and discredited the suggestion of harm, that emphasized on the need of well-designed randomized controlled trial to confirm the role of statins in COVID-19 patients.

Our study would help determine the potential therapeutic effect of the endothelial protocol as adjunct to mainstream management. This study seeks to further our knowledge in treating COVID-19 to ultimately improve clinical outcomes and reduce complications.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Lebanese American University Medical Center
• Treatments: Atorvastatin; Folic Acid; Nebivolol; Nicorandil; Vitamin B Complex

Criteria

Inclusion Criteria:

• Adults 18 years of age and above admitted for inpatient treatment of COVID-19 infection

• PCR-confirmed COVID-19 classified as mild, moderate or with severe disease as per the FDA.

With mild being a positive testing by standard RT-PCR assay or equivalent test and symptoms of mild illness with COVID-19 that could include fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, without shortness of breath or dyspnea. No clinical signs indicative of Moderate, Severe, or Critical Severity.

• Moderate defined as positive testing by standard RT-PCR assay or equivalent testing and symptoms of moderate illness which could include any symptom of mild illness or shortness of breath with exertion. Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate ≥ 20 breaths per minute, saturation of oxygen (SpO2) > 93% on room air at sea level, heart rate ≥ 90 beats per minute. No clinical signs indicative of Severe or Critical Illness Severity.

• Severe symptoms could include any symptom of moderate illness or shortness of breath at rest, or respiratory distress. Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory 468 rate ≥ 30 per minute, heart rate ≥ 125 per minute, SpO2 ≤ 93% on room air at sea level or 469 PaO2/FiO2 < 300.

• No criteria for Critical Severity.

• Eligible for or taking statin

Exclusion Criteria:

• Participant in another RCT

• Myocarditis

• Patients who are already on beta-blockers

Patients already on Nicorandil.

. Patients taking PDE5 inhibitors or Riociguat

.Shock as defined by SBP<90 for more than 30 minutes not responding to IV fluids with evidence of end organ damage.

.Severe bradycardia (<50 bpm).

.Heart block greater than first-degree (except in patients with a functioning artificial pacemaker).

.Decompensated heart failure.

.Sick sinus syndrome (unless a permanent pacemaker is in place).

.Severe hepatic impairment (Child-Pugh class C) or active liver disease.

.Unexplained persistent elevations of serum transaminases.

.Pregnancy or breastfeeding.

.Hypersensitivity to any of the medications.

• Can't take medications orally

• Patient refuses to participate