<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04456712</url>
  </required_header>
  <id_info>
    <org_study_id>ciprofloxacin and levofloxacin</org_study_id>
    <nct_id>NCT04456712</nct_id>
  </id_info>
  <brief_title>Effect of Ciprofloxacin Versus Levofloxacin on QTc-interval and Dysglycemia</brief_title>
  <official_title>Effect of Ciprofloxacin Versus Levofloxacin on QTc-interval and Dysglycemia in Diabetic and Non-Diabetic Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beni-Suef University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beni-Suef University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To compare intravenous levofloxacin and ciprofloxacin regarding their risk on the corrected&#xD;
      QT interval (QTc) prolongation and dysglycemia in diabetic and non-diabetic patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Fluoroquinolones represent an important class of antibacterial drug and they are used&#xD;
      worldwide.Fluoroquinolones are classified into generations according to the spectrum of&#xD;
      antimicrobial activities that targeted them.Fluoroquinolones may cause several side effects&#xD;
      as tendon rupture, central nervous toxicity, cardiovascular toxicity, gastrointestinal&#xD;
      toxicity, phototoxicity, disrupted glucose metabolism, skin disorders and hypersensitivity.&#xD;
      Ciprofloxacin, a second generation fluoroquinolone, is one of the most successful and widely&#xD;
      used compounds of fluoroquinolone. On the other hand, levofloxacin is a third generation&#xD;
      fluoroquinolone.&#xD;
&#xD;
      Diabetes mellitus (DM) is chronic disease and a serious of metabolic disorder associated with&#xD;
      the presence of hyperglycemia due to partial or complete insulin deficiency. Diabetes&#xD;
      mellitus is a major risk factor for cardiovascular diseases.&#xD;
&#xD;
      Fluoroquinolone class is associated with cardiac side effects as QTc prolongation. Some&#xD;
      agents of fluoroquinolones were withdrawn from market. However, cardiac adverse effects has&#xD;
      been developed with fluoroquinolones still in market. Members of fluoroquinolones class have&#xD;
      different effects on QT interval. The US FDA suggested that the risk and benefits ratio of&#xD;
      fluoroquinolones should be taken into consideration.&#xD;
&#xD;
      In addition to hyperglycemia events are more common with fluoroquinolones than with other&#xD;
      classes of antibiotics. The food and drug administration (FDA) confirmed the current warning&#xD;
      that fluoroquinolones may cause decrease in blood sugar especially in diabetic patients.&#xD;
      However, other study proved that fluoroquinolones may cause dysglycemic events in diabetic&#xD;
      and non-diabetic patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2018</start_date>
  <completion_date type="Actual">December 30, 2018</completion_date>
  <primary_completion_date type="Actual">November 30, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>fifty diabetic patients received intravenous levofloxacin 750 mg/24 hours. fifty diabetic patients received intravenous ciprofloxacin 400mg/12 hours. fifty non-diabetic patients received intravenous levofloxacin 750 mg/24 hours. fifty non-diabetic patients received intravenous ciprofloxacin 400mg/12 hours.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect of ciprofloxacin versus levofloxacin on QTc interval</measure>
    <time_frame>before starting antibiotic, after 24 hours, 72 hours from the first dose and after 72 hours from antibiotic cessation</time_frame>
    <description>change in QTc interval (QTc prolongation)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of ciprofloxacin versus levofloxacin on fasting blood glucose</measure>
    <time_frame>before starting antibiotic, after 24 hours, 72 hours from the first dose and after 72 hours from antibiotic cessation</time_frame>
    <description>change in fasting blood glucose (dysglycemia)</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">200</enrollment>
  <condition>QTc Prolongation, Hyperglycemia, Hypoglycemia</condition>
  <arm_group>
    <arm_group_label>ciprofloxacin for diabetic patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 diabetic patients received intravenous ciprofloxacin 400mg/12 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>levofloxacin for diabetic patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 diabetic patients received intravenous levofloxacin 750mg/24 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ciprofloxacin for non-diabetic patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 non-diabetic patients received intravenous ciprofloxacin 400mg/12 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>levofloxacin for non-diabetic patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 non-diabetic patients received intravenous levofloxacin 750mg/24 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ciprofloxacin 400 MG/200 ML Intravenous Solution</intervention_name>
    <description>antibiotic</description>
    <arm_group_label>ciprofloxacin for diabetic patients</arm_group_label>
    <arm_group_label>ciprofloxacin for non-diabetic patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levofloxacin 750 MG</intervention_name>
    <description>antibiotic</description>
    <arm_group_label>levofloxacin for diabetic patients</arm_group_label>
    <arm_group_label>levofloxacin for non-diabetic patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adult patient (male, female)&#xD;
&#xD;
          -  age from 18 to 70 years .&#xD;
&#xD;
          -  Be able to give an informed consent form after understanding for reasonable&#xD;
             explanation of clinical trial's purpose, contents and characteristics of clinical&#xD;
             drugs&#xD;
&#xD;
          -  Wiling to participate whole clinical trial periods&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Younger than 18 years or older than 70 years.&#xD;
&#xD;
          -  Has prolonged QTc before receiving therapy.&#xD;
&#xD;
          -  With a history of heart diseases.&#xD;
&#xD;
          -  Received class IA or III antiarrhythmic agents.&#xD;
&#xD;
          -  Received macrolide antibiotics.&#xD;
&#xD;
          -  With a history of quinolone allergy.&#xD;
&#xD;
          -  Pregnant and lactating women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ahmed A Elberry, professor</last_name>
    <role>Study Director</role>
    <affiliation>Faculty of medicine, Beni-Suef university, Beni-Suef, Egypt</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hazem S Hussein, MD</last_name>
    <role>Study Director</role>
    <affiliation>Faculty of medicine, Beni-Suef university, Beni-Suef, Egypt</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Raghda R Sayed, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Faculty of pharmacy, Beni-Suef university, Beni-Suef, Egypt</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beni-Suef university hospital</name>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>31357640</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25494485</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>30148925</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>29488552</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>June 30, 2020</last_update_submitted>
  <last_update_submitted_qc>June 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beni-Suef University</investigator_affiliation>
    <investigator_full_name>Nada Abd El-Hamed Saad Rezk</investigator_full_name>
    <investigator_title>clinical pharmacist</investigator_title>
  </responsible_party>
  <keyword>Levofloxacin, ciprofloxacin, QTc prolongation, dysglycemia.</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypoglycemia</mesh_term>
    <mesh_term>Hyperglycemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ciprofloxacin</mesh_term>
    <mesh_term>Levofloxacin</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>July 6, 2020</submitted>
    <returned>July 20, 2020</returned>
    <submitted>July 20, 2020</submitted>
    <returned>August 4, 2020</returned>
    <submitted>August 22, 2020</submitted>
    <returned>September 11, 2020</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04456712
org study id: ciprofloxacin and levofloxacin
nct id: NCT04456712
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
To compare intravenous levofloxacin and ciprofloxacin regarding their risk on the corrected
      QT interval (QTc) prolongation and dysglycemia in diabetic and non-diabetic patients.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: fifty diabetic patients received intravenous levofloxacin 750 mg/24 hours. fifty diabetic patients received intravenous ciprofloxacin 400mg/12 hours. fifty non-diabetic patients received intravenous levofloxacin 750 mg/24 hours. fifty non-diabetic patients received intravenous ciprofloxacin 400mg/12 hours.
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Effect of ciprofloxacin versus levofloxacin on QTc interval
time frame: before starting antibiotic, after 24 hours, 72 hours from the first dose and after 72 hours from antibiotic cessation
description: change in QTc interval (QTc prolongation)
measure: Effect of ciprofloxacin versus levofloxacin on fasting blood glucose
time frame: before starting antibiotic, after 24 hours, 72 hours from the first dose and after 72 hours from antibiotic cessation
description: change in fasting blood glucose (dysglycemia)
arm group label: ciprofloxacin for diabetic patients
arm group type: Experimental
description: 50 diabetic patients received intravenous ciprofloxacin 400mg/12 hours.
arm group label: levofloxacin for diabetic patients
arm group type: Experimental
description: 50 diabetic patients received intravenous levofloxacin 750mg/24 hours.
arm group label: ciprofloxacin for non-diabetic patients
arm group type: Experimental
description: 50 non-diabetic patients received intravenous ciprofloxacin 400mg/12 hours.
arm group label: levofloxacin for non-diabetic patients
arm group type: Experimental
description: 50 non-diabetic patients received intravenous levofloxacin 750mg/24 hours.
intervention type: Drug
intervention name: Ciprofloxacin 400 MG/200 ML Intravenous Solution
description: antibiotic
arm group label: ciprofloxacin for diabetic patients
arm group label: ciprofloxacin for non-diabetic patients
intervention type: Drug
intervention name: Levofloxacin 750 MG
description: antibiotic
arm group label: levofloxacin for diabetic patients
arm group label: levofloxacin for non-diabetic patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Ahmed A Elberry, professor
role: Study Director
affiliation: Faculty of medicine, Beni-Suef university, Beni-Suef, Egypt
last name: Hazem S Hussein, MD
role: Study Director
affiliation: Faculty of medicine, Beni-Suef university, Beni-Suef, Egypt
last name: Raghda R Sayed, PhD
role: Study Director
affiliation: Faculty of pharmacy, Beni-Suef university, Beni-Suef, Egypt
facility: 
country: Egypt
citation: 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.
PMID: 31357640
citation: 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.
PMID: 25494485
citation: 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.
PMID: 30148925
citation: 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.
PMID: 29488552
responsible party type: Principal Investigator
investigator affiliation: Beni-Suef University
investigator full name: Nada Abd El-Hamed Saad Rezk
investigator title: clinical pharmacist
mesh term: Hypoglycemia
mesh term: Hyperglycemia
mesh term: Ciprofloxacin
mesh term: Levofloxacin
submitted: July 6, 2020
returned: July 20, 2020
submitted: July 20, 2020
returned: August 4, 2020
submitted: August 22, 2020
returned: September 11, 2020