Clinical trial NCT05459389: Early Targeted Antibiotic Therapy in Patients With Sepsis
Official title: Efficacy of Early Targeted Antibiotic Therapy in Patients With Sepsis and Septic Shock
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Lead sponsor: Damanhour University
Sponsor class: OTHER
First posted: 2022-07-15
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomly allocated to antibiotic regimen guided by conventional culture technique (n=24) or targeted antibiotics therapy guided by resistance genotyping (n=24)
Primary purpose: TREATMENT

Brief summary: The aim of this study is to assess the efficacy of early targeted antibiotic therapy in patients with sepsis and septic shock using the new biomarker Sirtuin 1 and PCR for bacterial resistance detection.

The primary outcome is change in SOFA score (ΔSOFA) which will be calculated by subtracting the final SOFA score and sirtuin 1 level at 5 days from the corresponding initial value at enrollment.

Secondary outcomes included mortality rates, ventilator free days and length of icu stay.

Detailed description: * A prospective, single-center, open labeled, randomized interventional study
* Patients will be recruited from a private hospital in Alexandria
* Approval will be obtained from Research Ethics Committee of Faculty of Pharmacy, Damanhour University
* Fourty eight critically ill patients, with sepsis and septic shock according to the 2016 third international consensus definitions, will be included
* Patients with risk for Carbapenemase producing organisms:

  * Use of broad spectrum cephalosporins and/or carbapenems within the past three months
  * Polytrauma
  * Diabetes
  * Malignancy
  * Organ transplantation
  * Mechanical ventilation
  * Indwelling urinary or venous catheters
  * Overall poor functional status or severe illness
  * Residence in a long-term care facility(18-28).
* The baseline characteristics of the patients will be collected at the time of enrollment. The collected data included age, sex, ratio of septic shock to sepsis, ratio of ventilated to non-ventilated patients, source of infection, vital signs, laboratory data, arterial blood gas (ABG), APACHE II score, Glasgow Coma Scale score, and SOFA scores. The level of Procalcitonin (PCT) and Sirtuin-1 will also be measured at this time(29).
* Patients will be randomly allocated to antibiotic regimen guided by conventional culture technique (n=24) or targeted antibiotics therapy guided by resistance genotyping (n=24) (29, 30).
* Levels of Sirtuin1 will be detected using ELISA kits as prescribed by manufacturer.
* Traditional diagnostic microbiology techniques relying on the growth of organisms on appropriate culture media (Control group).
* Qualitative Multiplex pcr test will be used for rapid detection of carbapenemases genes (Intervention group)
* Statistical tests appropriate to the study will be conducted to evaluate significance of results
* Results, conclusion, discussion and recommendations will be given.

Eligibility criteria: Inclusion Criteria:

1. Male and female patients 18 years or older
2. A definite diagnosis of sepsis or septic shock according to the definition of the 2016 SCCM/ESICM task force.
3. Patients at risk for carbapenemase producing organisms

Exclusion Criteria:

1. Pregnant and lactating women
2. hematological disorders (e.g., leukemia, myelodysplastic syndrome, neoplastic metastases to bone marrow),
3. life-threatening diseases (e.g., malignant solid tumors), acquired immunodeficiency syndrome.
4. Lethal traumatic injury
5. Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score ≥34 (due to high predicted mortality of 80%)
6. Primary fungal or viral infections

Primary outcomes:
measure: Sirtuin1 (ng/ml)
timeFrame: 5 days
measure: SOFA (score)
timeFrame: 5 days
Secondary outcomes:
measure: mortality rates (%)
timeFrame: 5 days
measure: ventilator free days (days)
timeFrame: 5 days
measure: length of icu stay (Days)
timeFrame: 5 days
Other outcomes:
Locations:
city: Damanhūr
country: Egypt
facility: Rehab Hussein Werida
state: Elbehairah
Study officials:
affiliation: Damanhour University
name: Rehab H Werida, Ass. Prof.
role: STUDY_DIRECTOR
affiliation: Damanhour University
name: Noha Elbassiony
role: PRINCIPAL_INVESTIGATOR
affiliation: Damanhour University
name: Eman Momtaz
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Martinez ML, Plata-Menchaca EP, Ruiz-Rodriguez JC, Ferrer R. An approach to antibiotic treatment in patients with sepsis. J Thorac Dis. 2020 Mar;12(3):1007-1021. doi: 10.21037/jtd.2020.01.47.
citation: Bhattacharyya RP, Bandyopadhyay N, Ma P, Son SS, Liu J, He LL, Wu L, Khafizov R, Boykin R, Cerqueira GC, Pironti A, Rudy RF, Patel MM, Yang R, Skerry J, Nazarian E, Musser KA, Taylor J, Pierce VM, Earl AM, Cosimi LA, Shoresh N, Beechem J, Livny J, Hung DT. Simultaneous detection of genotype and phenotype enables rapid and accurate antibiotic susceptibility determination. Nat Med. 2019 Dec;25(12):1858-1864. doi: 10.1038/s41591-019-0650-9. Epub 2019 Nov 25.