Azithromycin Adverse ReactionNCT04699097
The Effect of Azithromycin Use on Conduction System of Heart in COVID-19 Positive Children
An observational study of Azithromycin Adverse Reaction and Covid19, run by Kayseri City Hospital at 1 site in Turkey (Türkiye).
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. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Azithromycin Adverse Reaction, Covid19, Long QT Syndrome
- What is being tested?
- Azithromycin
- Type of treatment
- Pill or oral medicine
- How many people
- 105 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Jul 2020to 1 Nov 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: children who recieved oral azithromycin therapy due to COVID 19 infection
Who may be able to join
- PCR positive COVID-19 patients
- Age<18 yearts
- Minimum 3 days oral Azithromycin therapy
- At least one ECG before and after treatment
Who cannot join
- parasitic ECG
- not having at least 1 ECG before or after treatment
- taking drugs other than hydroxychloroquine to prolong the QT interval
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Süleyman Sunkak
Kayseri, In the USA Or Canada, Please Select..., (554) 217-68
About this study
Official title: Azitromycin Use in COVID-19 Positive Pediatric Patients; Effect on Ventricle Repolarization
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.
Read the detailed 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).
- Conditions
- Azithromycin Adverse Reaction, Covid19, Long QT Syndrome
- Being tested
- Azithromycin
- Medical subject headings
- COVID-19, Long QT Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
250 mg tablet, 5 ml / 200 mg 30 ml suspension
| Study group | Role | What they receive |
|---|---|---|
| azytromycin | children who recieved azithromycin due to COVID 19 infection Receives: Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Before treatment-5th day of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2021
- Study start1 Jul 2020
- Primary completion1 Sep 2020
- Study completion1 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Azithromycin Adverse ReactionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kayseri City Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, süleyman sunkak, Kayseri City Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04699097
- Sponsor's protocol ID
- 139
- Status last verified
- Jan 2021
- First submitted
- 31 Dec 2020
- Last updated
- 7 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: share after 3 months
Publications
McMullan BJ, Mostaghim M. Prescribing azithromycin. Aust Prescr. 2015 Jun;38(3):87-9. doi: 10.18773/austprescr.2015.030. Epub 2015 Jun 1.
PubMed 26648627Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. RETRACTED: 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.
PubMed 32205204Schwartz 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.
PubMed 32510734Dogan 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.
PubMed 22696873
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Azitromycin Use in COVID-19 Positive Pediatric Patients; Effect on Ventricle Repolarization
- ClinicalTrials.gov ID
- NCT04699097
- Acronym / sponsor ID
- 139
- Conditions
- Azithromycin Adverse Reaction, Covid19, Long QT Syndrome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Kayseri City HospitalOther government
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 1 Sep 2020 (actual)
- Study completion
- 1 Nov 2020 (actual)
- First posted
- 7 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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).
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| azytromycin | – | Drug: Azithromycinchildren who recieved azithromycin due to COVID 19 infection |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- children who recieved oral azithromycin therapy due to COVID 19 infection
Key inclusion criteria (4 listed)
- PCR positive COVID-19 patients
- Age<18 yearts
- Minimum 3 days oral Azithromycin therapy
- At least one ECG before and after treatment
Key exclusion criteria (3 listed)
- parasitic ECG
- not having at least 1 ECG before or after treatment
- taking drugs other than hydroxychloroquine to prolong the QT interval
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azithromycin250 mg tablet, 5 ml / 200 mg 30 ml suspension | Drug | azytromycin |
Primary outcome
Effect of azitromycin on ventricle repolarization
Time frame: Before treatment-5th day of treatment
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2021.
- Background: PubMed 26648627McMullan BJ, Mostaghim M. Prescribing azithromycin. Aust Prescr. 2015 Jun;38(3):87-9. doi: 10.18773/austprescr.2015.030. Epub 2015 Jun 1.
- Background: PubMed 32205204Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. RETRACTED: 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.
- Background: PubMed 32510734Schwartz 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.
- Background: PubMed 22696873Dogan 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.
- Individual participant dataSharing planned: No. share after 3 months
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Azithromycin Adverse Reaction and Covid19, run by Kayseri City Hospital at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of azitromycin on ventricle repolarization (time frame: Before treatment-5th day of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04699097, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2021.