Procalcitonin to Shorten Antibiotics Duration in ICU Patients (ProShort)

Procalcitonin to Shorten Antibiotics Duration in ICU Patients- A China, Hong-Kong, Taiwan Multicenter Trial

The trial is aimed to show that implementation of a procalcitonin-guided antibiotics algorithm may result in shortened antibiotics course in ICU sepsis patients without inferior outcome as compared to the conventional therapy

Study Overview

• Status: Unknown
• Conditions: Sepsis
• Intervention / Treatment: Behavioral: Conventional treatment; Behavioral: Procalcitonin guided antibiotics treatment algorithm

Detailed Description

The duration of antibiotic therapy in patients with sepsis is largely empirical. An extended treatment course for up to two weeks is a common practice for patients with sepsis in the ICU, despite lack of evidence for this duration of therapy.

Procalcitonin (PCT) is a new biomarker that has high negative predictive value for systemic bacterial infection. The purpose of this trial is to evaluate whether serial PCT measurements can shorten antibiotic treatment duration in patients with sepsis in the ICU.

Specific Aims

1. To show that implementation of a procalcitonin-guided antibiotics stewardship algorithm may result in shortened antibiotics course in ICU sepsis patients
2. To show that implementation of a procalcitonin-guided antibiotics stewardship algorithm may not result in inferior outcome as compared to conventional therapy

• Study Type: Interventional
• Enrollment (Anticipated): 1700
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chien-Chang Lee, MD, MSc; Phone Number: +886-972-651951; Email: cclee100@gmail.com

Study Locations

• China
  • Beijing, China
    • Not yet recruiting
    • Department of Critical Care Medicine, The 301 People Liberation Army General Hospital
    • Principal Investigator: Chin Song, MD
  • Beijing, China
    • Recruiting
    • Emergency Department, Beijing Chao-Yang Hospital, Capital Medical University
    • Contact: Chunsheng Li, MD
    • Principal Investigator: Chunsheng Li, MD
  • Shanghai, China
    • Recruiting
    • Emergency Department, Ruijin Hospital, Jiaotong University, School of Medicine
    • Contact: Yiming Lu, MD
    • Principal Investigator: Yiming Lu, MD
  • Shanghai, China
    • Recruiting
    • Emergency Department, Xinhua Hospital, Jiaotong University School of Medicine
    • Principal Investigator: Shuming Pan, MD
  • Tianjin, China
    • Recruiting
    • Department of Critical Care Medicine, The General Hospital of Tianjin Medical University
    • Principal Investigator: Min Peng, MD
  • Xinjiang
    • Urumqi, Xinjiang, China
      • Recruiting
      • Department of Critical Care Medicine, The First Affiliated Hospital of Xinjiang Medical University
      • Principal Investigator: Shiangtai Yu, MD
• Hong Kong
  • Lai Chi Kok, Hong Kong
    • Not yet recruiting
    • Department of Pathology, Princess Margaret Hospita
    • Principal Investigator: Bosco Lam, MD
• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • Department of Emergency, National Taiwan University Hospital
    • Principal Investigator: Chien-Chang Lee, MD
    • Sub-Investigator: Ang Yuan, MD, PhD
    • Sub-Investigator: Hsien-Ho Lin, MD ScD
    • Sub-Investigator: Shan-Chewn Chang, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients with laboratory- or image-confirmed severe infection at admission or during stay in ICU will be eligible for inclusion.

Definition of laboratory- or image-confirmed severe infection:

1. Two or more of four Signs of Inflammation

   • Temperature > 38.3℃ or < 36℃
   • Heart rate > 90 beats/min
   • Respiratory rate > 20 breaths/min or PaCO2 < 32 mmHg
   • WBC > 12,000 cells/mm3, < 4000 cells/mm3, or > 10% bands
2. Initial Procalcitonin > 0.5 ng/mL
3. Presence of either laboratory or image evidence of infection

Laboratory evidence:

Sign of inflammation in urine, CSF, ascites, pleural effusion or local abscess

Image evidence:

Compatible findings on Chest X ray、ultrasound、CT、or MR image

Exclusion Criteria:

• Age less than 20 years
• Known pregnancy
• Presence of DNR order
• Expected ICU stay less than 3 days
• Neutropenia (ANC count < 500/mm3)
• Specific infections for which long-term antibiotic treatment is strongly recommended: lung abscess or empyema, bacterial meningitis, osteomyelitis, infective endocarditis, local abscess, mediastinitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional Treatment; Patients who will be randomized to arm 1 will receive antibiotic therapy with a duration based on conventional practice	Behavioral: Conventional treatment; Patients who will be randomized to arm 1 will receive antibiotic therapy with a duration based on conventional practice.
Experimental: procalcitonin-guided antibiotics treatment; Patients who will be randomized to arm 2 will receive antibiotics therapy with a duration based on procalcitonin-guided algorithm.	Behavioral: Procalcitonin guided antibiotics treatment algorithm; Patients who will be randomized to arm 2 will receive antibiotics therapy with a duration based on procalcitonin measurement on day 5, 7 and 9.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average antibiotics duration		28 days
28-day mortality rate	Safety endpoints	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
90-day all-cause mortality	90 days
Proportion of antibiotics use in both arms	28 days
Length of ICU stay	90 days
Recurrence of fever within 72 hours of antibiotics discontinuation	28 days
APACHE-II score or SOFA score	28 days
Reinfection between 72-hours and 28 days post antibiotics discontinuation	28 days
90-day infection related readmission rate	90 days

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Chinese PLA General Hospital; Ruijin Hospital; Beijing Chao Yang Hospital; Chongqing Medical University; Shanghai Jiao Tong University School of Medicine; Tianjin Medical University General Hospital; Princess Margaret Hospital, Hong Kong; Xinjiang Medical University
• Investigators: Principal Investigator: Chien-Chang Lee, MD, MSc, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): June 1, 2013

Study Registration Dates

• First Submitted: June 21, 2011
• First Submitted That Met QC Criteria: June 22, 2011
• First Posted (Estimate): June 23, 2011

Study Record Updates

• Last Update Posted (Estimate): November 27, 2012
• Last Update Submitted That Met QC Criteria: November 26, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: ICU; Procalcitonin; antibiotic; sepsis; antibiotic duration; Antibiotic treatment duration
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: 201101079RB