The Effect of Azithromycin Use on Conduction System of Heart in COVID-19 Positive Children

Covid19 Clinical Trial

Official title:

Azitromycin Use in COVID-19 Positive Pediatric Patients; Effect on Ventricle Repolarization

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04699097
• Other study ID #: 139
• Status: Completed
• Start date: July 1, 2020
• Est. completion date: November 1, 2020

Study information

• Verified date: January 2021
• Source: Kayseri City Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Azithromycin (AZ) is used in the pediatric group in COVID-19 diseas. It has been reported to cause prolongation in the QT interval in adult age group. The aim of this study is to evaluate the effect of AZ on ventricular repolarization in COVID-19 positive pediatric patients.

METHOD The study was conducted prospectively in July-August 2020. COVID-19 pediatric patients who received AZ treatment were included in the study. ECG was obtained before treatment and on the 1st, 3rd and 5th days after the treatment. Measurements were made with Image J program®. QTmax, QTmin, Tp-emax, Tp-emin intervals were measured. QTcmax, QTcmin, Tp-ecmax, Tp-ecmin, QTcd, Tp-ecd, and QTc / Tp-ec ratios were calculated with Bazett formula.

Description:

The study was prospectively conducted between June 2020 and August 2020. Children hospitalized in Kayseri City Hospital Pediatric Infection Clinic for coronavirus disease and receiving oral AZ treatment were included in the study. Approval was obtained from the local ethics committee. Written informed consent was obtained from the patients and their families. AZ treatment was given as oral 10 mg / kg (maximum 500 mg) on Day 1, followed by 5 mg / kg (maximum 250 mg) on Days 2-5 once a daily. A 12-lead ECG was obtained before the treatment and on the 1st, 3rd and 5th days of the treatment. Patients who did not have at least one ECG before and after the treatment and whose QT and Tp-Te intervals could not be calculated due to excessively parasitic ECG were not included in the study.

ECG was obtained with a GE Mac 2000® device with a paper speed of 25 mm / sec, 10 mv / mm amplitude standard. ECGs were scanned with a scanner and transferred to the computer as JPEG format. QT, Tp-Te intervals were measured by a pediatric cardiologist using ImageJ® program.

Intervals between two consecutive R waves were defined as RR interval. QT interval was defined as the interval from the beginning of the QRS complex to the end of the T wave.

The end of the T wave was defined as intersection of the terminal limb of the T wave with the isoelectric baseline. The longest and the shortest QT intervals across 12 leads were defined as the maximum QT (QTmax) and the minimum QT (QTmin) intervals, respectively. They were corrected according to heart rate by using the Bazett Formula and defined as corrected QTmax (QTmaxc) and corrected QTmin (QTminc), respectively. Bazett formula was preferred to provide uniformity and enable comparison with other studies [Bazett: QTc = QT/(RR)1/2]. QTc dispersion (QTcd) was defined as the difference between QTmaxc and QTminc.

For the T-wave peak to T-wave end interval (Tp-e) measurement, time interval between peak of T wave, ie the time point in which T wave had highest amplitude and end of T wave which also was defined as the crossing point of T wave and isoelectric line was noted as a function of time. Tp-e was also corrected according to heart rate and referred as Tp-ec. The longest and the shortest Tp-e intervals were defined as the maximum Tp-e (Tp-emax) and the minimum Tp-e (Tp-emin) intervals, respectively. Tp-e dispersion (Tp-ed) was defined as the difference between Tp-emax and Tp-emin. Tp-e/QT and Tp-ec/QTc ratios were calculated as maximum and minimum seperately.13 STATISTICAL ANALYSIS The normality of distribution of the ECG measurements and ratios were determined with Kolmogorov-Smirnov test. Descriptive statistics are expressed as mean ± standard deviation (SD) for continuous variables and proportion for categorical variables. Friedman test was used to evaluate repetitive ECG measurements before and after treatment days. P value < 0.05 was considered as statistically significant. All statistical analyses were carried out with the Statistical Package for Social Science for Windows version 22.0 (SPSS Inc., Chicago, IL).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: November 1, 2020
• Est. primary completion date: September 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

Inclusion Criteria:

• PCR positive COVID-19 patients

• Age<18 yearts

• Minimum 3 days oral Azithromycin therapy

• At least one ECG before and after treatment

Exclusion Criteria:

• parasitic ECG

• not having at least 1 ECG before or after treatment

• taking drugs other than hydroxychloroquine to prolong the QT interval

Related Conditions & MeSH terms

• Azithromycin Adverse Reaction
• Covid19
• Long QT Syndrome

Intervention

Drug:
• Azithromycin
250 mg tablet, 5 ml / 200 mg 30 ml suspension

Locations

Country	Name	City	State
Turkey	Süleyman Sunkak	Kayseri	In The USA Or Canada, Please Select...

Sponsors (1)

Lead Sponsor	Collaborator
Kayseri City Hospital

Country where clinical trial is conducted

Turkey, 

References & Publications (4)

Dogan U, Yavas G, Tekinalp M, Yavas C, Ata OY, Ozdemir K. Evaluation of the acute effect of palonosetron on transmural dispersion of myocardial repolarization. Eur Rev Med Pharmacol Sci. 2012 Apr;16(4):462-8. — View Citation

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20. — View Citation

McMullan BJ, Mostaghim M. Prescribing azithromycin. Aust Prescr. 2015 Jun;38(3):87-9. Epub 2015 Jun 1. Review. — View Citation

Schwartz RA, Suskind RM. Azithromycin and COVID-19: Prompt early use at first signs of this infection in adults and children, an approach worthy of consideration. Dermatol Ther. 2020 Jul;33(4):e13785. doi: 10.1111/dth.13785. Epub 2020 Jul 12. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of azitromycin on ventricle repolarization	In the superficial ECG, the QTc, Tp-Tec intervals and Tp-Tec / QTc ratios represent ventricular repolarization. QTc measurement above 0.45 sec is a risk factor for malignant arrhythmia. The significant increase in these intervals and rates compared to previous measurements indicates an increased risk of malignant arrhythmia.	Before treatment-5th day of treatment