Optimizing Antibiotic Dosing Regimens for the Treatment of Infection Caused by Carbapenem Resistant Enterobacteriaceae

NCT ID: NCT04516395

Last Updated: 2020-08-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-30

Study Completion Date

2021-04-30

Brief Summary

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The purpose of this study is to evaluate the treatment outcomes in patients with CRE infections.

Detailed Description

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Antibiotic resistance is one of the major problems because of global burden. Resistant pathogens are non-susceptible to available antibiotics, causing of high clinical mortality (clinical impact) and high budget (economic impact), whereas new antibiotics in drug development are fewer. Carbapenem-Resistant Enterobacteriaceae (CRE) are categorized into one of the critical groups in World Health Organization's lists. In Thailand, the spread of CRE have been risen continuously since 2011.

Diverse actions are designed to address antibiotic resistance with limited resources, known as antimicrobial stewardship programs (ASPs). Dose-optimization by using PK/PD (Pharmacokinetics/Pharmacodynamics) application is recommendation of supplemental strategies in clinical routine practice. The benefit of the strategy is to reduce inappropriate antibiotic use and provide minimum resistance as well as maximum the success of clinical treatment.

Antibiotic combination regimens have a role for the CRE treatment. However, current evidence in clinical study is not concluded which the best or optimal combined antibiotics are. The reasons may be that combined antibiotics often vary among different sites of infection, causative pathogens, the patterns of local antimicrobial susceptibility and patient comorbidity. As the results, the antibiotic combination regimens for the treatment any infections caused by CRE is needed for further investigation. The anticipated result is to fill the limited data of the appropriate antibiotic regimens for individual Thai patients.

Conditions

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Drug Resistance Carbapenem-Resistant Enterobacteriaceae Infection Sepsis Septic Shock Critical Illness Clinical Outcomes Treatment Outcomes

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

According to the model, it divided into two parts - retrospective chart review and prospective data collection. Single independent patient group will be divided two parts depending on over a period of time. The patients in the retrospective part received a standard treatment become a control group, while the patients in the prospective part received the intervention become an experimental group.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Optimal antibiotic combination regimens

The patients in the groups will be given the optimal antibiotic combination regimens.

Group Type EXPERIMENTAL

Combined antibiotic regimens

Intervention Type OTHER

Combined antibiotic combinations defined as the optimal antibiotic combination regimens which are created from in vitro study and the application of PK/PD.

Standard antibiotic regimens

The patients in the groups will be given the standard antibiotic regimens.

Group Type OTHER

Standard antibiotic regimens

Intervention Type OTHER

Standard antibiotic regimens defined as the antibiotic regimens which are generally given to the patients following to the hospital protocol.

Interventions

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Combined antibiotic regimens

Combined antibiotic combinations defined as the optimal antibiotic combination regimens which are created from in vitro study and the application of PK/PD.

Intervention Type OTHER

Standard antibiotic regimens

Standard antibiotic regimens defined as the antibiotic regimens which are generally given to the patients following to the hospital protocol.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Any patients are diagnosed any diseases caused by CRE infection by physicians at Phramongkutklao hospital during 1/4/2018 to 30/4/2021.
2. Any patients are more than 18 years old.
3. Any patients have at least 1 criterion as following 3.1 Any patients have at least 2 of the signs and symptoms of Systemic inflammatory response syndrome (SIRS), including

* Fever (temperature \> 38 °C) or hypothermia (temperature \< 36°C)
* Tachypnea (heart rate \> 90 beats per minute)
* Respiratory rate \> 20 beats per minute or Paco2 \< 32 mm Hg (4.3 kPa)
* White blood cell count \> 12,000 cells per millilitre (leukocytosis) or \< 4,000 cells per milliliter (leukopenia) 3.2. Any patients are diagnosed with sepsis or have ≥ 2 points of Sequential Organ Failure Assessment (SOFA) Score or qSOFA (Quick SOFA) Score.

3.3. Any patients are diagnosed with septic shock or are received vasopressors (eg, dopamine, norepinephrine, epinephrine, vasopressin, phenylephrine), mean arterial pressure (MAP) \< 65 mm Hg, and lactate \> 2 mmol/L (18 mg/dL) 3.4 Any patients are received mechanical ventilation 3.5 Any patients are admitted at ICU ward.

Exclusion Criteria

1. Patients are breast-feeding or pregnancy.
2. Patients are insufficient or incomplete information on the medical electronic record such as patients transferred.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Phramongkutklao College of Medicine and Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wichai Santimaleeworagun

Role: PRINCIPAL_INVESTIGATOR

Silpakorn University

Locations

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Phramongkutklao hospital

Bangkok, , Thailand

Site Status

Countries

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Thailand

Central Contacts

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Wichai Santimaleeworagun, PhD

Role: CONTACT

663547600

Facility Contacts

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Parnrada Nulsopapon

Role: primary

667633120

References

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Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.

Reference Type RESULT
PMID: 26903338 (View on PubMed)

Tillotson G. A crucial list of pathogens. Lancet Infect Dis. 2018 Mar;18(3):234-236. doi: 10.1016/S1473-3099(17)30754-5. Epub 2017 Dec 21. No abstract available.

Reference Type RESULT
PMID: 29276050 (View on PubMed)

Barlam TF, Cosgrove SE, Abbo LM, MacDougall C, Schuetz AN, Septimus EJ, Srinivasan A, Dellit TH, Falck-Ytter YT, Fishman NO, Hamilton CW, Jenkins TC, Lipsett PA, Malani PN, May LS, Moran GJ, Neuhauser MM, Newland JG, Ohl CA, Samore MH, Seo SK, Trivedi KK. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016 May 15;62(10):e51-77. doi: 10.1093/cid/ciw118. Epub 2016 Apr 13.

Reference Type RESULT
PMID: 27080992 (View on PubMed)

Asin-Prieto E, Rodriguez-Gascon A, Isla A. Applications of the pharmacokinetic/pharmacodynamic (PK/PD) analysis of antimicrobial agents. J Infect Chemother. 2015 May;21(5):319-29. doi: 10.1016/j.jiac.2015.02.001. Epub 2015 Feb 12.

Reference Type RESULT
PMID: 25737147 (View on PubMed)

Rodriguez-Bano J, Gutierrez-Gutierrez B, Machuca I, Pascual A. Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae. Clin Microbiol Rev. 2018 Feb 14;31(2):e00079-17. doi: 10.1128/CMR.00079-17. Print 2018 Apr.

Reference Type RESULT
PMID: 29444952 (View on PubMed)

Tamma PD, Goodman KE, Harris AD, Tekle T, Roberts A, Taiwo A, Simner PJ. Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia. Clin Infect Dis. 2017 Feb 1;64(3):257-264. doi: 10.1093/cid/ciw741. Epub 2016 Nov 9.

Reference Type RESULT
PMID: 28013264 (View on PubMed)

Demidenko E, Miller TW. Statistical determination of synergy based on Bliss definition of drugs independence. PLoS One. 2019 Nov 25;14(11):e0224137. doi: 10.1371/journal.pone.0224137. eCollection 2019.

Reference Type RESULT
PMID: 31765385 (View on PubMed)

Sheu CC, Chang YT, Lin SY, Chen YH, Hsueh PR. Infections Caused by Carbapenem-Resistant Enterobacteriaceae: An Update on Therapeutic Options. Front Microbiol. 2019 Jan 30;10:80. doi: 10.3389/fmicb.2019.00080. eCollection 2019.

Reference Type RESULT
PMID: 30761114 (View on PubMed)

Gutierrez-Gutierrez B, Salamanca E, de Cueto M, Hsueh PR, Viale P, Pano-Pardo JR, Venditti M, Tumbarello M, Daikos G, Canton R, Doi Y, Tuon FF, Karaiskos I, Perez-Nadales E, Schwaber MJ, Azap OK, Souli M, Roilides E, Pournaras S, Akova M, Perez F, Bermejo J, Oliver A, Almela M, Lowman W, Almirante B, Bonomo RA, Carmeli Y, Paterson DL, Pascual A, Rodriguez-Bano J; REIPI/ESGBIS/INCREMENT Investigators. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis. 2017 Jul;17(7):726-734. doi: 10.1016/S1473-3099(17)30228-1. Epub 2017 Apr 22.

Reference Type RESULT
PMID: 28442293 (View on PubMed)

Other Identifiers

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Q011h/63

Identifier Type: -

Identifier Source: org_study_id

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