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Trial details
Managing Endothelial Dysfunction in COVID-19: A Randomized Clinical Trial at the Lebanese American University Medical Center- Rizk Hospital
Current status:
Approved
|
Date registered:
08/02/2021
|
Date last updated:
07/02/2021
Trial version(s)
Current: 28/10/2020
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2021014651
Protocol number
000000
MOH registration number
000000
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
28/10/2020
Primary sponsor
LAUMCRH
Primary sponsor: Country of origin
Lebanon
Public title
Managing Endothelial Dysfunction in COVID-19: A Randomized Clinical Trial at the Lebanese American University Medical Center- Rizk Hospital
Acronym
MEDIC-LAUMCRH
Scientific title
Managing Endothelial Dysfunction in COVID-19: A Randomized Clinical Trial at the Lebanese American University Medical Center- Rizk Hospital
Acronym
MEDIC-LAUMCRH
Brief summary of the study: English
Endothelial dysfunction has been proven to be one of the major mechanisms by which COVID-19 is causing illness to the human body. We aim to study the effectiveness and tolerability of a medication protocol aimed at improving endothelial dysfunction in COVID-19 infected patients. The Protocol contains a statin (atorvastatin) a beta blocker (nebivolol) combined with L-arginine, nicorandil and folic acid. The endothelium in summary is monolayer lining the arteries, veins and microvasculature. The endothelium hence plays a major role in homeostasis with interactive roles in blood pressure regulation, anti-coagulation and immune protection Moreover, it is thus relevant to note that the most common comorbidities that present with COVID-19 such as hypertension, diabetes, obesity and old age are all underlined by pre-existing endothelial damage or dysfunction. As such, endothelial dysfunction and oxidative stress and their relation to the manifestation and progression of COVID-19 infections has gain significant traction in recent publications. This breakthrough exposes several causes of endothelial dysfunction which include direct lining attack, hypoxia, cytokine storm and suppressed endothelial nitric oxide synthase (eNOS) with concomitant nitric oxide deficiency. Several studies have emphasized the role of NO signaling as a major regulator of vascular tone and its antioxidant, anti-inflammatory and antithrombotic activity. For example, augmenting the production of NO and its bioavailability by nicorandil has been proposed as a potential treatment in patients with COVID 19. Nicorandil (a vasodilatory agent composed of N-[2-hydroxyethyl]-nicotinamide nitrate) used among patients with acute heart failure emergencies However, it has never been tested in patients with cardiovascular complications resulting from COVID 19 . Statins are cardioprotective in nature with recent reports showing that they can be beneficial in COVID-19 . An important mechanism via which Statins may improve endothelial function include increasing the production of NO and subsequent vasodilation effect, along with its established major anti-inflammatory and anti-oxidant properties . Nebivolol, a cardio-selective beta blocker has also shown non-adrenergic vasodilating properties via the release of NO along with antioxidative and anti-atherosclerotic activities. Furthermore, eNOS overexpression leads to an increase in NO formation only when the BH4 synthase GTP-cyclohydrolase 1 (GCH-1) is alsoup-regulated. So, Folic Acid and L-arginine will be given to supplement our patients with BH4 . We hypothesize that its administration along with the other previously mentioned agents would improve endothelial function in patients suffering from COVID 19 via a cumulative increase in the bioavailability of Nitric Oxide (NO), and thus improving patients’ outcomes by demonstrating a clinical improvement as measured by the six-category ordinal scale. The secondary endpoints will include improvement in laboratory parameters, assessment for need of invasive mechanical ventilation, length of ICU stay, length of hospital stay, length of need for mechanical ventilation, all-cause mortality, and occurrence of side effects. This hypothesis was formulated based several studies which expressed that endothelial dysfunction and oxidative stress are one of the major pathophysiological mechanism at the root of multiple causes of mortality and morbidity in COVID-19 patients. However, currently no randomized clinical trial evaluating this concept exists. Therefore, to provide the scientific evidence for the endothelial dysfunction protocol as part of the treatment regimen for SARS-CoV-2 infection, a trial is warranted.
Brief summary of the study: Arabic
تهدف هذه الدراسة الى تقييم قدرة وفعالية العلاج في تحسين الخلل البطاني للأوعية الدموية عند المرضى المصابين بـ COVID-19 من خلال تقييم أولي للتحسن السريري حسب المؤشرات والمقياس الترتيبي ذي الفئات الست. ستشمل نقاط التقييم الثانوية :الحاجة إلى التنفس الاصطناعي، طول مدة الإقامة في وحدة العناية المركزة ، مدة الإقامة في المستشفى ، مدة الحاجة إلى التنفس الاصطناعي، حدوث الوفاة لجميع الأسباب، وحدوث اثار جانبية للعلاج.
Health conditions/problem studied: Specify
COVID-19 and the cardiovascular system We will aim at treating endothelial dysfunction caused by covid -19 virus by an endothelial protocol to try to improve the patient's outcome
Interventions: Specify
Randomized controlled tiral with 2 arms one intervention arm and the other is a placebo arm
Key inclusion and exclusion criteria: Inclusion criteria
INCLUSION CRITERIA: Firstly, participants must be in-patient adults 18 years of age and above. Secondly, having PCR-confirmed COVID-19 classified as mild, moderate or severe disease as per the FDA and admitted to the hospital for inpatient treatment as per the standard of care, 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 include respiratory rate ≥ 20 breaths per minute, saturation of oxygen (SpO2) > 93% on room air at sea level, heart rate ≥ 90 beats per minute without 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 include respiratory rate ≥ 30 per minute, heart rate ≥ 125 per minute, SpO2 ≤ 93% on room air at sea level or PaO2/FiO2 < 300. No criteria for Critical Severity.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
99
Key inclusion and exclusion criteria: Exclusion criteria
EXCLUSION CRITERIA: Patients unable to tolerate oral medications. Patients who are already on beta-blockers, statins or Nicorandil, PDE5 inhibitors, Riociguat.. In addition to those with shock as defined by SBP<90 for more than 30 minutes not responding to IV fluids with evidence of end organ damage. Patients with severe bradycardia (<50 bpm) and heart block greater than first-degree (except in patients with a functioning artificial pacemaker) should be definitely excluded, along with those who suffer from decompensated heart failure and sick sinus syndrome (unless a permanent pacemaker is in place). Severe hepatic impairment (Child-Pugh class C) or active liver disease are absolute reasons not to be included especially those with unexplained persistent elevations of serum transaminases. Pregnancy or breastfeeding and hypersensitivity to any of the medications are to be excluded as well. Myocarditis. Acute pulmonary edema. Hypovolemia. Patients enrolled in a different randomized study and/or COVID interventional study.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Active
Study phase
3
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
Yes, Lebanon
Name of IMP
Nicorandil Atorvastatin L-Arginine Folic Acid Nebivolol
Year of authorization
2018
Month of authorization
1
Type of IMP
Others
Type of IMP: Specify
Pharmaceutical Medication
Pharmaceutical class
Beta blocker Statin Dietary supplement Cornoary vasodilator
Therapeutic indication
Endothelial and Microvascular dysfunction in COVID-19
Therapeutic benefit
1- Scale for clinical improvement 2-Objective measures of sustained improvement (e.g., return to room air or baseline oxygen requirement) 3- Need for invasive mechanical ventilation 4- Length of ICU stay 5- Length of hospital Stay 6- Length of need of mechanical ventilation 7- All cause mortality 8- Occurrence of side effects
Biospecimen retention
None retained
Biospecimen description
None will be used
Target sample size
66
Actual enrollment target size
80
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
15/11/2020
Date of study closure: Type
Anticipated
Date of study closure: Date
31/12/2020
Recruitment status
Pending
Date of completion
01/02/2021
IPD sharing statement plan
Yes
IPD sharing statement description
No personal data will be shared.
Additional data URL
none
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Sources of Monetary or Material Support
Name
Self Funding by LAUMCRH
Secondary Sponsors
Name
NA
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Kamal
Matli
LAUMCRH
Lebanon
9613439675
matlikamal@gmail.com
LAUMCRH
Scientific
Kamal
Matli
LAUMCRH
Lebanon
9613439675
matlikamal@gmail.com
LAUMCRH
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Lebanese American University Medical Center Rizk Hospital
Dr. Georges Ghanem
Cardiology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Lebanese American University- University Medical Center Rizk Hospital
04/01/2021
Karmen Baroudy
karmen.baroudy@lau.edu.lb
01200800
Countries of Recruitment
Name
Lebanon
Health Conditions or Problems Studied
Condition
Code
Keyword
COVID-19
2-Propanol (T51.2)
COVID-19
Interventions
Intervention
Description
Keyword
Medical therapy for COVID-19 infection
Endothelial dysfunction will be targeted by our medications to improve patient outcome in COVID-19 infection
Endothelial dysfunction and COVID-19
Placebo or L-arginine
3g po TID
Supplement
Placebo or Folic Acid
5 mg po OD
Supplement
Placebo or Atorvastatin
40 mg po OD
medication
Placebo or Nicorandil
10 mg po BID
Medication
Placebo or Nebivolol
2.5-5 mg po OD
Medication
Primary Outcomes
Name
Time points
Measure
Clinical improvement was defined as improvement of at least two points from the baseline from date of intervention administration until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 1-month status on the six-category ordinal scale. This scale contains the subsequent categories: (1) death (2) hospital admission requiring invasive mechanical ventilation (3) hospital admission, requiring non-invasive positive pressure ventilation (4) hospital admission, requiring oxygen (5) hospital admission, not requiring oxygen (6) discharge.
we will follow our patients for a total of 28 days .
Clinical Improvement
Key Secondary Outcomes
Name
Time points
Measure
II. Secondary outcomes: Time Frame: from date of intervention administration until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 1 month: Objective measures of sustained improvement (e.g., return to room air or baseline oxygen requirement) on day 7, 14 and 28 3- Need for invasive mechanical ventilation 4- Length of ICU stay 5- Length of hospital Stay 6- Length of need of mechanical ventilation 7- All cause mortality 8- Occurrence of side effects
we will follow the patients for a total of 28 days
Clinical Endpoint
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial