Effect of Ciprofloxacin Versus Levofloxacin on QTc-interval and Dysglycemia

Effect of Ciprofloxacin Versus Levofloxacin on QTc-interval and Dysglycemia in Diabetic and Non-Diabetic Patients.

To compare intravenous levofloxacin and ciprofloxacin regarding their risk on the corrected QT interval (QTc) prolongation and dysglycemia in diabetic and non-diabetic patients.

Study Overview

• Status: Completed
• Conditions: QTc Prolongation, Hyperglycemia, Hypoglycemia
• Intervention / Treatment: Drug: Ciprofloxacin 400 MG/200 ML Intravenous Solution; Drug: Levofloxacin 750 MG

Detailed Description

Fluoroquinolones represent an important class of antibacterial drug and they are used worldwide.Fluoroquinolones are classified into generations according to the spectrum of antimicrobial activities that targeted them.Fluoroquinolones may cause several side effects as tendon rupture, central nervous toxicity, cardiovascular toxicity, gastrointestinal toxicity, phototoxicity, disrupted glucose metabolism, skin disorders and hypersensitivity. Ciprofloxacin, a second generation fluoroquinolone, is one of the most successful and widely used compounds of fluoroquinolone. On the other hand, levofloxacin is a third generation fluoroquinolone.

Diabetes mellitus (DM) is chronic disease and a serious of metabolic disorder associated with the presence of hyperglycemia due to partial or complete insulin deficiency. Diabetes mellitus is a major risk factor for cardiovascular diseases.

Fluoroquinolone class is associated with cardiac side effects as QTc prolongation. Some agents of fluoroquinolones were withdrawn from market. However, cardiac adverse effects has been developed with fluoroquinolones still in market. Members of fluoroquinolones class have different effects on QT interval. The US FDA suggested that the risk and benefits ratio of fluoroquinolones should be taken into consideration.

In addition to hyperglycemia events are more common with fluoroquinolones than with other classes of antibiotics. The food and drug administration (FDA) confirmed the current warning that fluoroquinolones may cause decrease in blood sugar especially in diabetic patients. However, other study proved that fluoroquinolones may cause dysglycemic events in diabetic and non-diabetic patients.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Beni-suef university Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patient (male, female)
• age from 18 to 70 years .
• Be able to give an informed consent form after understanding for reasonable explanation of clinical trial's purpose, contents and characteristics of clinical drugs
• Wiling to participate whole clinical trial periods

Exclusion Criteria:

• Younger than 18 years or older than 70 years.
• Has prolonged QTc before receiving therapy.
• With a history of heart diseases.
• Received class IA or III antiarrhythmic agents.
• Received macrolide antibiotics.
• With a history of quinolone allergy.
• Pregnant and lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ciprofloxacin for diabetic patients; 50 diabetic patients received intravenous ciprofloxacin 400mg/12 hours.	Drug: Ciprofloxacin 400 MG/200 ML Intravenous Solution; antibiotic
EXPERIMENTAL: levofloxacin for diabetic patients; 50 diabetic patients received intravenous levofloxacin 750mg/24 hours.	Drug: Levofloxacin 750 MG; antibiotic
EXPERIMENTAL: ciprofloxacin for non-diabetic patients; 50 non-diabetic patients received intravenous ciprofloxacin 400mg/12 hours.	Drug: Ciprofloxacin 400 MG/200 ML Intravenous Solution; antibiotic
EXPERIMENTAL: levofloxacin for non-diabetic patients; 50 non-diabetic patients received intravenous levofloxacin 750mg/24 hours.	Drug: Levofloxacin 750 MG; antibiotic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of ciprofloxacin versus levofloxacin on QTc interval	change in QTc interval (QTc prolongation)	before starting antibiotic, after 24 hours, 72 hours from the first dose and after 72 hours from antibiotic cessation
Effect of ciprofloxacin versus levofloxacin on fasting blood glucose	change in fasting blood glucose (dysglycemia)	before starting antibiotic, after 24 hours, 72 hours from the first dose and after 72 hours from antibiotic cessation

Collaborators and Investigators

• Sponsor: Beni-Suef University
• Investigators: Study Director: Ahmed A Elberry, professor, Faculty of medicine, Beni-Suef university, Beni-Suef, Egypt; Study Director: Hazem S Hussein, MD, Faculty of medicine, Beni-Suef university, Beni-Suef, Egypt; Study Director: Raghda R Sayed, PhD, Faculty of pharmacy, Beni-Suef university, Beni-Suef, Egypt

Publications and helpful links

General Publications

• Mathews B, Thalody AA, Miraj SS, Kunhikatta V, Rao M, Saravu K. Adverse Effects of Fluoroquinolones: A Retrospective Cohort Study in a South Indian Tertiary Healthcare Facility. Antibiotics (Basel). 2019 Jul 27;8(3):104. doi: 10.3390/antibiotics8030104.
• Lu ZK, Yuan J, Li M, Sutton SS, Rao GA, Jacob S, Bennett CL. Cardiac risks associated with antibiotics: azithromycin and levofloxacin. Expert Opin Drug Saf. 2015 Feb;14(2):295-303. doi: 10.1517/14740338.2015.989210. Epub 2014 Dec 10.
• Granados J, Ceballos M, Amariles P. [Hypo or hyperglycemia associated with fluoroquinolone use]. Rev Med Chil. 2018 May;146(5):618-626. doi: 10.4067/s0034-98872018000500618. Spanish.
• Gonzalez M C, Rosales C R, Pavez D, Fuenzalida LM, Soto A, Perez R, Perez J, Araos R, Pinto ME. [Safety of fluoroquinolones: risks usually forgotten for the clinician]. Rev Chilena Infectol. 2017 Dec;34(6):577-582. doi: 10.4067/S0716-10182017000600577. Spanish.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2018
• Primary Completion (ACTUAL): November 30, 2018
• Study Completion (ACTUAL): December 30, 2018

Study Registration Dates

• First Submitted: June 30, 2020
• First Submitted That Met QC Criteria: June 30, 2020
• First Posted (ACTUAL): July 2, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 2, 2020
• Last Update Submitted That Met QC Criteria: June 30, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Levofloxacin, ciprofloxacin, QTc prolongation, dysglycemia.
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Hypoglycemia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Ciprofloxacin; Levofloxacin; Ofloxacin
• Other Study ID Numbers: ciprofloxacin and levofloxacin

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No