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AzTrials

Antibiotic Side EffectPhase 4NCT05742295

Prevention of Cefoperazone-induced Coagulopathy

A Phase 4 study testing Vitamin K in people with Antibiotic Side Effect, run by Helwan University at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Antibiotic Side Effect
What is being tested?
Vitamin K
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
1 siteEgypt
Study dates
25 Feb 2023to 5 Oct 2023
Phase
Phase 4
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Egypt1 site

  • 6-October Hospital

    Giza

Other trials in Egypt

About this study

Official title: 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.

Read the 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.

Being tested
Vitamin K
Keywords
Coagulopathy, Cefoperazone, Vitamin K, Cefoperazone/sulbactam
Medical subject headings
Hemostatic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vitamin KDrug

    Coadministration of vitamin K with the first dose of cefoperazone/sulbactam

Study groups in NCT05742295
Study groupRoleWhat they receive
Intervention groupExperimentalvitamin K is used as a prophylactic dose to prevent cefoperazone/sulbactam coagulopathy.
Receives: Drug: Vitamin K
Control groupNo interventionNot described

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with changes in INR level

    comparing INR level between baseline INR (before starting the antibiotic) and during the treatment with the antibiotic

    Measured: During the duration of cefoperazone/sulbactam treatment up to 2 weeks

Secondary outcomes (1)

  1. Number of Participants with bleeding incidence

    Internal bleeding as hematemesis or melena

    Measured: During the duration of cefoperazone/sulbactam treatment up to 2 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2023
  2. Study start25 Feb 2023
  3. Primary completion5 Oct 2023
  4. Study completion5 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05742295
Sponsor's protocol ID
Vit. K for SULBinCo
Status last verified
Oct 2023
First submitted
10 Feb 2023
Last updated
10 Oct 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Cai Z, Yang W, He Y, Chen Q, Wang S, Luo X, Wang X. Cefoperazone/Sulbactam-Induced Abdominal Wall Hematoma and Upper Gastrointestinal Bleeding: A Case Report and Review of the Literature. Drug Saf Case Rep. 2016 Dec;3(1):2. doi: 10.1007/s40800-016-0025-9.

    PubMed 27747682

  • Schentag JJ, Welage LS, Grasela TH, Adelman MH. Determinants of antibiotic-associated hypoprothrombinemia. Pharmacotherapy. 1987;7(3):80-6. doi: 10.1002/j.1875-9114.1987.tb03522.x.

    PubMed 3306622

  • Schentag JJ, Welage LS, Williams JS, Wilton JH, Adelman MH, Rigan D, Grasela TH. Kinetics and action of N-methylthiotetrazole in volunteers and patients. Population-based clinical comparisons of antibiotics with and without this moiety. Am J Surg. 1988 May 31;155(5A):40-4. doi: 10.1016/s0002-9610(88)80210-1.

    PubMed 3163900

  • Allison PM, Mummah-Schendel LL, Kindberg CG, Harms CS, Bang NU, Suttie JW. Effects of a vitamin K-deficient diet and antibiotics in normal human volunteers. J Lab Clin Med. 1987 Aug;110(2):180-8.

    PubMed 3598347

  • Mendes R, Policarpo S, Fortuna P, Alves M, Virella D, Heyland DK; Portuguese NUTRIC Study Group. Nutritional risk assessment and cultural validation of the modified NUTRIC score in critically ill patients-A multicenter prospective cohort study. J Crit Care. 2017 Feb;37:45-49. doi: 10.1016/j.jcrc.2016.08.001. Epub 2016 Aug 10.

    PubMed 27621112

  • Fouda R, Soliman MS, ElAnany MG, Abadeer M, Soliman G. Prevalence and risk factors of MRSA, ESBL and MDR bacterial colonization upon admission to an Egyptian medical ICU. J Infect Dev Ctries. 2016 Apr 28;10(4):329-36. doi: 10.3855/jidc.6798.

    PubMed 27130993

  • Abdelkader MM, Aboshanab KM, El-Ashry MA, Aboulwafa MM. Prevalence of MDR pathogens of bacterial meningitis in Egypt and new synergistic antibiotic combinations. PLoS One. 2017 Feb 16;12(2):e0171349. doi: 10.1371/journal.pone.0171349. eCollection 2017.

    PubMed 28207768

  • Talaat M, El-Shokry M, El-Kholy J, Ismail G, Kotb S, Hafez S, Attia E, Lessa FC. National surveillance of health care-associated infections in Egypt: Developing a sustainable program in a resource-limited country. Am J Infect Control. 2016 Nov 1;44(11):1296-1301. doi: 10.1016/j.ajic.2016.04.212. Epub 2016 Jun 20.

    PubMed 27339791

  • Hu HR. Fatal Vitamin K-Dependent Coagulopathy Associated with Cefoperazone/Sulbactam: A Case Report. Drug Saf Case Rep. 2019 Jun 14;6(1):6. doi: 10.1007/s40800-019-0100-0.

    PubMed 31201572

  • Wang W, Liu Y, Yu C, Tan J, Xiong W, Dong D, Li S, Zhang R, Li J, Wu Y, Zong Z, Su N, Zou K, Wu G, Sun X. Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study. Expert Opin Drug Saf. 2020 Mar;19(3):339-347. doi: 10.1080/14740338.2020.1713090. Epub 2020 Jan 27.

    PubMed 31914329

  • Park GH, Kim S, Kim MS, Yu YM, Kim GH, Lee JS, Lee E. The Association Between Cephalosporin and Hypoprothrombinemia: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2019 Oct 16;16(20):3937. doi: 10.3390/ijerph16203937.

    PubMed 31623191

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Vitamin K in people with Antibiotic Side Effect, run by Helwan University at 1 site in Egypt.

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 1 inclusion and 6 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 10 Oct 2023. 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 Egypt. 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Number of Participants with changes in INR level (time frame: During the duration of cefoperazone/sulbactam treatment up to 2 weeks). 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 NCT05742295, which also lists 11 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 10 Oct 2023.

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