RESEARCH PROPOSAL

PREVALENCE OF THE RISK FACTORS FOR QT INTERVAL PROLONAGTION IN

HOSPITALIZED COVID-19 PATIENTS

SUBMITTED BY: Muhammad Raffay Farrukh

Pharm.D. Student
Department of Pharmacy
COMSATS University Islamabad
Abbottabad Campus

Qasim Khan, PhD

Assistant Professor
RESEARCH SUPERVISOR: Department of Pharmacy
COMSATS University Islamabad
Abbottabad Campus

FIELD SUPERVISOR:

INTRODUCTION
The QT interval is the period between the beginning of the QRS complex and the end of the T
wave [1]. Thus, it is the estimate of the time interval between the earliest ventricular
depolarization and the latest ventricular repolarization [1]. Because the QT interval is affected by
changes in the heart rate, corrections are usually made to the QT interval for these changes (QTc)
[2]. The Committee for Proprietary Medicinal Products (CPMP) has suggested ranges for normal
(i.e., men less than 430 msec, women less than 450 msec), borderline (i.e., men 430 to 450 msec,
women 450 to 470 msec), and prolonged (i.e., men greater than 450 msec, women greater than

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470 msec) QTc intervals [3]. Many drugs including antiarrhythmic, antipsychotic, antihistamine,
antidepressant, antifungal, fluoroquinolone, macrolide, antimalarial, diuretics, anticancer,
antihypertensive, antiviral and antiemetic agents are associated with QT-prolongation [4].
Patients with electrolyte abnormalities, use of certain drugs [5-7] and drug-drug interactions are
considered to be at higher risk to QT interval prolongation. Drug-drug interactions can increase
this risk, either by a pharmacodynamics mechanism (cumulative effect of two QT prolonging
drugs) or a pharmacokinetic mechanism (reducing the metabolism of a QT prolonging drug) [8].
The medications carrying risk for QT interval prolongation are often prescribed either alone or
concomitantly in COVID-19 patients and this factor need to be considered in order to prevent
their associated adverse consequences. Therefore, work is needed in this area because data are
scarce regarding this issue in Pakistan that would have focused on QT interval prolongation and
associated factors in COVID-19 patients.

AIMS AND OBJECTIVES

The main aim and objectives of this study are to:
 Identify the prescribing pattern of QT interval prolonging drugs.
 Determine the frequency of various risk factors that carry the potential to prolong QT and/or
cause torsade de pointes (TdP).
 Explore the frequency of drug-drug interactions (QT-DDIs) causing QT interval
prolongation.
 Identify the prevalence and predictors of QT interval prolongation in COVID-19 patients.
METHODOLOGY
Study Design and Data Collection
A cross-sectional design will be used involving collection of data from medical records of
patients, admitted to medical ward of the hospital. Following data will be obtained from medical
records of patients: age, gender, serum electrolytes levels, ECG results, diagnosis, comorbid
illnesses and a complete list of prescribed medications.

Inclusion Criteria
In this study, the following inclusion criteria were used:

 Clinical profiles of hospitalized patients admitted to the medical ward.

 Age >18 years.
 Both male and female patients.
 Patients diagnosed with any kind of disease.

Exclusion Criteria

 Patients’ profiles will be excluded if they lack any relevant information required for the
study such as patient’s age, gender, symptoms, diagnosis and medication therapy
provided in the hospital.
 Age <18 years
 Pregnancy

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Measurement of the corrected QT interval (QTc)

The QTc interval will be measured by the Bazett’s formula which is the most commonly used
formula in clinical settings. The formula is as follows:

QTc = QT interval/ RR1/2

Sample Size
The following formula has been used for estimation of sample size:
n = Z2 P (1-P) / d2
Where n is sample size, Z is Z-statistic for a level of confidence, P anticipated prevalence
proportion and d is margin of error. Based on the anticipated prevalence of 58.7; 5% margin of
error; and 95% confidence level, a minimum sample size of 373 is obtained by above formula.

Data Analysis
Data will be analyzed to find out the frequency of drugs causing QT interval prolongation. For
this purpose, “Credible Meds List” (www.qtdrugs.org) will be used as a reference list.
The potential drug-drug interactions causing QT interval prolongation will be screened by
various databases such as:
o Micromedex Database
o LexiComp Database
o Drug Interactions Facts
o http://medicine.iupui.edu/clinpharm/ddis/
Various cardiac and non-cardiac risk factors responsible for QT interval prolongation will also
be evaluated.

Statistical Analysis
In statistical analysis, continuous variables such as age, number of prescribed drugs and serum
electrolytes will be reported as mean ± standard deviation and categorical variables such as
gender, severity-levels of DDIs and diagnosis will be expressed as frequencies and percentage.
Association between QT interval prolongation and various risk factors will be assessed by
logistic regression analysis to calculate odds ratios (ORs) and their 95% confidence intervals
(CIs). For this study, p-value of 0.05 or less will be considered statistically significant. SPSS for
Windows version 25 (SPSS, Inc., Chicago, IL, USA) will be used for all statistical analyses.

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REFERENCES
1. Thomas, M., J. Maconochie, and E. Fletcher, The dilemma of the prolonged QT interval
in early drug studies. British journal of clinical pharmacology, 1996. 41(2): p. 77-81.

2. Malik, M. and A.J. Camm, Evaluation of drug-induced QT interval prolongation. Drug

Safety, 2001. 24(5): p. 323-351.

3. Owens, R.C., Risk Assessment for Antimicrobial Agent‐Induced QTc Interval

Prolongation and Torsades de Pointes. Pharmacotherapy: The Journal of Human
Pharmacology and Drug Therapy, 2001. 21(3): p. 301-319.

4. CredibleMeds: Arizona Center for Research and Therapeutics (AZCERT), Available at

www.crediblemeds.com. Accessed Date: March 15, 2022.

5. Lepeschkin, E. and B. Surawicz, The duration of the QU interval and its components in
electrocardiograms of normal persons. American heart journal, 1953. 46(1): p. 9-20.

6. Bernardi, M., et al., Q‐T interval prolongation in cirrhosis: Prevalence, relationship with
severity, and etiology of the disease and possible pathogenetic factors. Hepatology, 1998.
27(1): p. 28-34.

7. Vandael, E., et al., Frequency of use of QT-interval prolonging drugs in psychiatry in

Belgium. International journal of clinical pharmacy, 2014. 36(4): p. 757-765.

8. Armahizer, M.J., et al., Drug-drug interactions contributing to QT prolongation in

cardiac intensive care units. Journal of critical care, 2013. 28(3): p. 243-249.