Prevention of Cefoperazone-induced Coagulopathy

October 5, 2023 updated by: Hebatallah Ali Abdeen, Helwan University

Preventing Cefoperazone/Sulbactam Induced Coagulopathy in Critically Ill Egyptian Patients: Efficacy of Vitamin K Prophylactic Doses

Evaluating the effect of prophylactic doses of vitamin K in preventing the adverse effect of cefoperazone/sulbactam induced coagulopathy in critically ill patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

One of the most challenging issues in the intensive care unit is treating multidrug-resistant (MDR) bacterial infections weighing benefit to risk ratio. MDR bacterial infection in ICU is a major public health problem and the main cause of mortality in ICUs in Egypt. A study published in the American Journal of Infection Control pointed out that the prevalence of MDR bacterial infections in the ICU was 54%.

Cefoperazone is a 3rd generation cephalosporin antibiotic covering many Gram-positive and Gram-negative bacteria, sulbactam is a beta-lactamase inhibitor which is used in combination with many antibiotics to overcome beta-lactamase producing bacteria, therefore the combination of cefoperazone/sulbactam has activity against MDR gram-negative bacteria. On the other hand, cefoperazone has been shown to have the adverse effects of inducing coagulopathy which is reported in many case reports and retrospective cohort studies. In most cases, coagulopathy events occur within a few days from the start of using cefoperazone/sulbactam, therefore the ICU staff was obliged to discontinue the antibiotic and choose another alternative leading to increasing the risk of resistant bacteria and treatment failure. Therefore, discontinuing the antibiotic due to its serious adverse events will lead to poor outcomes, more bacterial resistance, and more cost therapeutic plans for treating the infection and managing the severe adverse drug events which have been occurred such as bleeding. There are 2 mechanisms for cefoperazone-induced coagulopathy. The first the mechanism is related to N-methylthiotetrazole (NMTT), a side chain in cefoperazone molecule, which is responsible for the inhibition of a vitamin K-dependent carboxylation process leading to antagonizing blood clotting factors. The the second mechanism is antibiotics, in general, kill the normal flora in the gut which produce vitamin K. This cefoperazone/sulbactam-induced coagulopathy is not found in healthy volunteers or patients with adequate vitamin K activity, therefore, could consider cefoperazone/sulbactam-induced coagulopathy in critically ill patients, as related to nutritional status of these patients specifically with regard to vitamin K. This study aimed at studying the effect of co-administration of prophylactic doses of vitamin k during the administration of cefoperazone/sulbactam to keep the normal daily requirements of vitamin k, therefore preventing coagulopathy.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Giza, Egypt
        • 6-October Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ICU admitted patients on treatment or prophylactic doses of cefoperazone/sulbactam.

Exclusion Criteria:

  • Patients' aged <18 years
  • Pregnancy or breastfeeding women
  • Active bleeding or bleeding disorder
  • Patients having an abnormal baseline coagulation profile.
  • Patients administer total parenteral nutrition with regular vitamin k supplements.
  • Refusal to sign the written informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control group
Experimental: Intervention group
vitamin K is used as a prophylactic dose to prevent cefoperazone/sulbactam coagulopathy.
Drug: Vitamin K
Coadministration of vitamin K with the first dose of cefoperazone/sulbactam

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with changes in INR level
Time Frame: During the duration of cefoperazone/sulbactam treatment up to 2 weeks
comparing INR level between baseline INR (before starting the antibiotic) and during the treatment with the antibiotic
During the duration of cefoperazone/sulbactam treatment up to 2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with bleeding incidence
Time Frame: During the duration of cefoperazone/sulbactam treatment up to 2 weeks
Internal bleeding as hematemesis or melena
During the duration of cefoperazone/sulbactam treatment up to 2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Helwan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 25, 2023

Primary Completion (Actual)

October 5, 2023

Study Completion (Actual)

October 5, 2023

Study Registration Dates

First Submitted

February 10, 2023

First Submitted That Met QC Criteria

February 22, 2023

First Posted (Actual)

February 23, 2023

Study Record Updates

Last Update Posted (Estimated)

October 9, 2023

Last Update Submitted That Met QC Criteria

October 5, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Vit. K for SULBinCo

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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