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Trial registered on ANZCTR


Registration number
ACTRN12612000601831
Ethics application status
Approved
Date submitted
31/05/2012
Date registered
4/06/2012
Date last updated
26/06/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
A pilot study of procalcitonin-based algorithms to guide antibiotics treatment in secondary peritonitis after surgery
Scientific title
A pilot study of procalcitonin-based algorithms to guide post-operative antibiotics treatment to improve duration of post-operative antibiotics exposure and cost-effectiveness in secondary peritonitis after surgery.
Secondary ID [1] 280594 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Does PCT-based algorithms to guide antibiotic therapy reduce the risk of antibiotics exposure in secondary peritonitis who will receive emergency surgery for acute abdomen without compromising clinical outcomes? 286597 0
Condition category
Condition code
Infection 286870 286870 0 0
Other infectious diseases
Surgery 286871 286871 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment plan:
All patients who fulfill the inclusion/exclusion criteria will receive empiric antibiotics treatment (rocephin 1gram intravenous given every 12 hours and metronidazole 500mg intravenous infusion every 8 hours) pre-operation and immediately post-operation. Infection specialists blinded to this project will routinely review the justification of antibiotics treatment including choices and duration in every patient. The in-charge physicians will decide whether to discontinue antibiotics according to the algorithm and clinical conditions or extend the antibiotics treatment if clinically needed.

PCT algorithm:
Antibiotic treatment will be discontinued if clinical signs of infection improved and the PCT value is either <1.0 ng/ml or decreases to less than 80% of the peak post-operative concentration over 3 postoperative days.

PCT and biomarkers measurement:
PCT levels will be obtained pre-operation, post-operative day1, 3, 5, 7, and before discharge by central lab in Chang-Gung Memorial Hospital (CGMH)-Keelung branch. The additional levels will be ordered by physicians after one week if clinically needed. Besides, plasma samples drawn by patients on pre-operation, post-operative day1, 3, 5, 7, and before discharge will be stored until analysis of liquid chromatography coupled tandem mass spectrometry (LC-MS/MS).

PCT-assays
Measuring Range: The BRAHMS PCT KRYPTOR assay measures concentrations between 0.02 and 5000 ng/ml (0.02 to 50 ng/ml directly and up to 5000 ng/ml after sample dilution).
Precision: BRAHMS PCT KRYPTOR shows a high precision in the determination of serum/plasma PCT concentrations. The intra-assay CV and the inter-assay CV are 2-3% on the whole PCT concentration range.
Intervention code [1] 284984 0
Treatment: Drugs
Intervention code [2] 284998 0
Early detection / Screening
Comparator / control treatment
The control patients will be obtained from medical records from 2010-2011 as historical controls.
Control group
Historical

Outcomes
Primary outcome [1] 287224 0
Duration of antibiotics exposure (days) will be assessed from medical records data.
Timepoint [1] 287224 0
Post-operative period to discharge.
Follow-up 3 months after discharge.
Primary outcome [2] 287225 0
Serious adverse events and adverse events will be assessed by clinically.

Serious adverse events:
Death from any causes is considered as a serious adverse event (SAE).

Adverse events attributions
ICU re-admission for any reason, disease-specific complications (i.e., persistence or development of intra-abdominal infections or abscess, and re-operation) and any intra-abdominal infectious complications in need of further antibiotics treatment after termination of antibiotics according to the studied PCT algorithms are defined as the adverse events (AE).
Timepoint [2] 287225 0
Post-opertative period to discharge.
Follow-up 3 months after discharge.
Secondary outcome [1] 297661 0
The mdical records data will be obtained for cost-effectiveness analysis.
Timepoint [1] 297661 0
Cost of antibiotics and procalcitonin assays during admission will be recorded. Statistical analysis will be conducted at the end of study.

Eligibility
Key inclusion criteria
Patients more than 20 years old who will receive emergency abdominal operations with sepsis due to secondary peritonitis are eligible for enrollment.
Minimum age
20 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who meet one or more of the following criteria will be excluded: (a) patients who are moribund (life expectance not expected to be > 72 hours because of imminent death) (b) patients with liver cirrhosis, Child’s class B and C liver disease (c) patients with profound septic shock under treatment of high dose inotropic agents (d) pre-existing infection underwent antibiotics treatment (e) multiple traumatized patients with unstable hemodynamic status (f) patients or their family will not participate in this study (g) immunocompromised patients such as HIV infection, long term steroids treatment, post-chemotherapy (h) pregnant women.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Consecutive enrollment by one surgeon.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 4341 0
Taiwan, Province Of China
State/province [1] 4341 0

Funding & Sponsors
Funding source category [1] 285358 0
Hospital
Name [1] 285358 0
Chang Gung Memorial Hospital, Keelung
Address [1] 285358 0
No. 222, Mai-Chin Road, Keelung 20401
Country [1] 285358 0
Taiwan, Province Of China
Primary sponsor type
Hospital
Name
Chang Gung Memorial Hospital, Keelung
Address
No. 222, Mai-Chin Road, Keelung 20401
Country
Taiwan, Province Of China
Secondary sponsor category [1] 284207 0
None
Name [1] 284207 0
Address [1] 284207 0
Country [1] 284207 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287365 0
Institutional Ethics Committee of Chang Gung Foundation
Ethics committee address [1] 287365 0
Ethics committee country [1] 287365 0
Taiwan, Province Of China
Date submitted for ethics approval [1] 287365 0
Approval date [1] 287365 0
10/04/2012
Ethics approval number [1] 287365 0
100-4574C

Summary
Brief summary
Peritonitis is one of the most important etiologies resulting in abdominal sepsis leading to considerable morbidity and mortality. However, there is still no adequate evidence-based data about the optimal duration of antibiotics (AB) treatment for moderate to severe complicated intra-abdominal infections after abdominal surgery. Prolonged duration of AB therapy can increase the risk of developing multidrug-resistant strains as well as adverse effects of AB and treatment associated costs. A systematic review showed that procalcitonin (PCT) levels were more sensitive and more specific than C-reactive protein (CRP) levels for differentiating bacterial from non-infective causes of inflammation. PCT improves the clinical diagnosis of sepsis in critically-ill patients and patients with community-acquired pneumonia. In patients with lower respiratory tract infections, a strategy of PCT guidance AB therapy compared with standard guidelines resulted in similar rates of adverse outcomes, as well as lower rates of antibiotic exposure and AB-associated adverse effects. Some small studies in surgical intensive unit demonstrated that PCT-based algorithms may reduce AB exposure without compromising clinical outcomes. We design this pilot study to investigate the feasibility and safety of PCT-based algorithms to guide post-operative AB therapy in secondary peritonitis. We will prospectively enroll 30 patients in this study for one year period. Appropriate historical control of the same kind of patients will be collected from hospital based databases. To investigate predictive and prognostic value of novel biomarkers, we will also explore the potential biomarkers of sepsis including plasma gelsolin and sphingolipids using liquid chromatography coupled tandem mass spectrometry method. In this study, we expect to shorten and optimize the duration of AB therapy in secondary peritonitis after surgery without compromising clinical outcomes, provide more information about novel biomarkers, and provide standardized proteomic methods to detect them.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34246 0
Dr Ting Shuo Huang
Address 34246 0
No. 222 Mai-Chin Road, Keelung 20401, Taiwan
Country 34246 0
Taiwan, Province Of China
Phone 34246 0
+886-2-24313131 Ext: 2625
Fax 34246 0
Email 34246 0
huangts@adm.cgmh.org.tw
Contact person for public queries
Name 17493 0
Dr Ting-Shuo Huang
Address 17493 0
7F, No. 222, Mai-Chin Road, Keelung 20401
Country 17493 0
Taiwan, Province Of China
Phone 17493 0
+886-2-24313131-2625
Fax 17493 0
Email 17493 0
huangts@adm.cgmh.org.tw
Contact person for scientific queries
Name 8421 0
Dr Ting-Shuo Huang
Address 8421 0
7F, No. 222, Mai-Chin Road, Keelung 20401
Country 8421 0
Taiwan, Province Of China
Phone 8421 0
+886-2-24313131-2625
Fax 8421 0
Email 8421 0
huangts@adm.cgmh.org.tw

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary