Dose Optimization by Pharmacokinetic/Pharmacodynamic of Antibiotics to Improve Clinical Outcome of Carbapenem Resistant Klebsiella Pneumoniae Bloodstream Infections in Critically Ill Patients at Phramongkutklao Hospital

• Sponsor: Phramongkutklao College of Medicine and Hospital (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05862402
• Collaborator: Silpakorn University (Other)
• Enrollment: 76
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 13.8
• Patients Per Site Per Month: 5.5

Study Details

Study Description

Brief Summary

The patients who infected with Carbapenem resistant Klebsiella pneumoniae were high mortality rate. Appropriate antibiotics therapy adjusted by Pharmacokinetic/Pharmacodynamic plays an important role in determining outcomes in Critically ill patients. Consequently, standard antibiotics dose may not be adequate to achieve pharmacokinetic/pharmacodynamic target in Critically ill patients. The purpose of this study is to compare the clinical outcomes between the critically ill patients who received antibiotics dose adjusted by pharmacokinetic/pharmacodynamic using Monte Carlo simulation and historical critically ill patients who received antibiotics from standard practice.

Condition or Disease	Intervention/Treatment	Phase
Carbapenem Resistant Klebsiella Pneumoniae	Drug: Dose-adjustment by PKPD	Phase 4

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 76 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective study compare historical controlled studyProspective study compare historical controlled study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Dose Optimization by PK/PD of Antibiotics to Improve Clinical Outcome of CRKP Bloodstream Infections in Critically Ill Patients and in Vitro Study of Monotherapy, Combination Therapy and Molecular Biology of Drug Resistance at Phramongkutklao Hospital: Prospective, Historical Controlled Study
• Anticipated Study Start Date: May 7, 2023
• Anticipated Primary Completion Date: May 31, 2024
• Anticipated Study Completion Date: Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention group Dose antibiotics adjusted by pharmacokinetic and pharmacodynamic using Monte Carlo simulation	Drug: Dose-adjustment by PKPD; Dose-adjustment by pharmacokinetic and pharmacodynamic using Monte Carlo simulation; Other Names: Antibiotics: Ceftazidime-Avibactam or Combination antibiotics (eg. Meropenem-Colistin, Imipenem-Colistin, Tigecycline-Amikacin, Tigecycline-Gentamicin, Tigecycline-Meropenem or Tigecycline-Colistin)
No Intervention: Control group Dose antibiotics from standard care

Outcome Measures

Primary Outcome Measures

1. Mortality [14 day]

   Alive or death

Secondary Outcome Measures

1. Mortality [30 days]

   Alive or death

2. Microbiological cure rate [14 days]

   Evaluated culture of bloodstream

3. Hospital length of stay [With in 30 days]

   Time interval (day) from hospital admission (after enrolled) to hospital discharge or death from any cause

4. ICU length of stay [With in 30 days]

   Time interval (day) from ICU admission (after enrolled) to ICU discharge or death from any cause

5. Clinical cure rate [Through treatment completion or with in 30 days]

   Evaluated sign and symptoms of infection or culture no growth

6. Duration of vasopressor or Inotropic agents [With in 30 days]

   Time interval (day) from time of vasopressor or Inotropic agents initiation to time to vasopressor or Inotropic agents discontinuation

7. Duration of ventilator [Assessed with in 30 days]

   Time interval (day) of ventilator

8. Ventilator free day [30 days]

   Day alive and free of ventilator

9. Vasopressor or Inotropic drug free day [30 days]

   Day alive and free of vasopressor or inotropic drug

10. Procalcitonin [14 days]

    Evaluated serum procalcitonin

11. Adverse event [Day 0, 5, 7 and finish course of Antibiotics or discharge]

    Evaluated side effect (eg. seizure, liver impairment, renal impairment)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 20 years and older who admitted at Phramongkutklao Hospital

2. Patients who was diagnosed blood stream infection with CRKP between April 10th, 2023 to March 31st, 2024 (Prospective study) and January 1st, 2012 to March 31st, 2023 (Retrospective study); Historical group

3. Patients who had signs and symptoms at least 1 criteria following:

3.1. Patients who had signs and symptoms of Systemic Inflammatory Response Syndrome (SIRS) at least 2 criteria:

• Temperature above 38 oC or below 36 oC

• Heart rate more than 90 beats/min

• Respiratory rate more than 20 /min or PaCO2 less than 32 mmHg (4.3 kPa)

• White blood cell more than 12,000 cell/mm3 or less than 4,000 cell/mm3 3.2. Patients who was diagnosed sepsis or SOFA score or qSOFA score at least 2 score 3.3. Patients who was diagnosed septic shock or who had hypotension with adequate fluid and need for vasopressor to maintain mean arterial pressure over 65 mmHg and serum lactate above 2 mmol/L

1. Patients who received antibiotics at least 48 hours which are as follow:

• Ceftazidime-Avibactam or

• Combination antibiotics (eg. Meropenem-Colistin, Imipenem-Colistin, Tigecycline-Amikacin, Tigecycline- Gentamicin, Tigecycline-Meropenem or Tigecycline-Colistin)

Exclusion Criteria:

1. Patients who were pregnancy or breastfeeding

2. Patients who had drug allergy (eg. Ceftazidime-Avibactam, Tigecycline, Amikacin, Gentamicin, Imipenem, Meropenem or Colistin)

3. Patients who not to received resuscitation.

4. Patients who were end stage cancer.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phramongkutklao Hospital	Ratchathewi	Bangkok	Thailand	10400

Sponsors and Collaborators

• Phramongkutklao College of Medicine and Hospital
• Silpakorn University

Investigators

• Study Chair: Sujareenoot Suya, PharmD, Faculty of Pharmacy, Silpakorn University
• Study Director: Weerayuth Saelim, BCP, Faculty of Pharmacy, Silpakorn University
• Study Director: Wichai Santimaleeworagun, PhD, Faculty of Pharmacy, Silpakorn University
• Study Director: Worapong Nasomsong, MD, Phramongkutklao College of Medicine and Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Phramongkutklao College of Medicine and Hospital
• ClinicalTrials.gov Identifier: NCT05862402
• Other Study ID Numbers: PMK-0008
• First Posted: May 17, 2023
• Last Update Posted: May 17, 2023
• Last Verified: Apr 1, 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Phramongkutklao College of Medicine and Hospital: Antibiotics; Dose optimization; Clinical outcome; CRKP; Critically ill
• Additional relevant MeSH terms: Pneumonia; Sepsis; Klebsiella Infections; Critical Illness; Anti-Bacterial Agents; Gentamicins; Meropenem; Imipenem; Amikacin; Ceftazidime; Colistin; Tigecycline; Avibactam; Antibiotics, Antitubercular

Study Results

No Results Posted as of May 17, 2023