Antibiotic Treatment Duration (7 vs 14 Days) Comparison in Blood Stream Infection Causes by Enterobacteriaceae (SHORTEN)

Phase 4, Randomized, Controlled Multicentric, Open-label Clinical Trial to Prove That the 7 Day Course of Treatment for Enterobacteriaceae Bacteremia is More Efficient and Equally Safe Than 14 Day Scheme

The antimicrobial crisis is a real problem. Infections produced by multiresistant bacteria are becoming more and more frequent, and available antimicrobial agents are usually scarce. Reducing the duration of antimicrobial treatments is one of the most efficient measures to control the antibiotic pressure and to optimise the use of these agents.

Bloodstream infections produced by Enterobacteria (EB) are very frequent, but the optimal duration of antibiotics to treat them is unknown, as long as no clinical trials have been specifically developed to answer this question.

Basing on expert opinions, the Infectious Diseases Society pf America (IDSA) recommends the bacteremia by EB secondary to vascular catheter infections to be treated for 7 to 14 days. This represents a variability of up to 100%. No recommendations have been published regarding the duration of treatment of bacteremia from other sources.

The objective of this project is to prove that the 7-day course of treatment for EB bacteremia is more efficient and equally safe than the 14-day scheme.

Study Overview

• Status: Completed
• Conditions: Enterobacteriaceae Infections; Bloodstream Infection
• Intervention / Treatment: Other: 7 days course of antibiotic treatment; Other: 14 days course of antibiotic treatment

Detailed Description

To achieve theses objectives, we propose this randomized, multicentric clinical trial with a superiority design on the duration of antimicrobial treatment for EB bacteremia in adult patients.

• Study Type: Interventional
• Enrollment (Actual): 238
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Córdoba, Spain, 14004
    • University Hospital Reina Sofia
  • Málaga, Spain, 29010
    • Universitary Hospital Málaga
  • Seville, Spain, 41007
    • University Hospital Virgen Macarena
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocío

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Adults patients (equal or over 18 years old)
• Primary or secondary bloodstream infection produced by enterobacteriaceae
• Source of bacteremia properly controlled or expect to be properly controlled in the next 24 hours (i.e. bacteremia produced by infected vascular catheter, abscess, obstruction of the biliary or urinary tract).
• Patients able to understand the objectives of the clinical trial and informed consent signed.

Exclusion Criteria:

• Pregnancy
• Post-chemotherapy neutropenia expected to persist more than 7 days.
• Source of bacteremia uncontrolled at inclusion period or in the following 24 hours. The source will be considered as uncontrolled if the bacteremia is secondary to a suppurative infection potentially removable, if no action has been taken to eradicate it, including: bacteremia by vascular not removed catheter, cholangitis secondary to not derived obstruction of the biliary tract, deep abscess not drained, pyohydronephrosis without derivation of the urinary tract.
• Bacteremia secondary to infective endocarditis, bone and joint infections, or neurosurgical infections, which may require prolonged antimicrobial therapy
• Bacteremia due to enterobacteriaceae resistant to carbapenemics.
• Polymicrobial bacteremia including microorganisms different to enterobacteriaceae.
• Patients with no expectations of survival in the next 48 hours of inclusion.

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
Experimental: 7 days course of antibiotic treatment; Accepted antibiotic indicated for enterobacteriaceae infections, according to sensibility test performed and daily practice protocols or local guidelines.	Other: 7 days course of antibiotic treatment; Standard antibiotic treatment approved for enterobacteraciae infections; Other Names: Antibiotics with approved indication
Active Comparator: 14 days course of antibiotic treatment; Accepted antibiotic indicated for enterobacteriaceae infections, according to sensibility test performed and daily practice protocols or local guidelines.	Other: 14 days course of antibiotic treatment; Standard antibiotic treatment approved for enterobacteraciae infections; Other Names: Antibiotics with approved indication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days of antimicrobial treatment	To prove that 7-days course of antibiotic therapy is more efficient than 14-days course when treating Enterobacteriaceae bacteremia, in terms of number of days at the end of follow up.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse reactions related to antimicrobial treatment	To prove that 7-days course of antibiotic therapy is as safe as a 14-days course in terms of : Rate of adverse effects including: adverse reactions to drugs, superinfections by resistant bacteria or diarrhea by Clostridium difficile, mortality, relapse of the infection	28 days
Cure of bacteremia	Clinical and microbiological cure	28 days
Procalcitonin levels	To analyze the utility of procalcitonin as a biomarker to decide the end of the antimicrobial treatment of Enterobacteriaceae bacteremia	7-days and 14-days

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Investigators: Study Director: Jose Molina Gil-Bermejo, MD. PhD, Hospitales Universitarios Virgen del Rocío

Publications and helpful links

Helpful Links

• This organization is formed by 16 Spanish leading research groups in the field, is public funded by Spanish Carlos III Institute and co-financed by European Development Regional Fund (ERDF)

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): December 2, 2016
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: August 5, 2014
• First Submitted That Met QC Criteria: March 23, 2015
• First Posted (Estimate): March 27, 2015

Study Record Updates

• Last Update Posted (Actual): March 13, 2017
• Last Update Submitted That Met QC Criteria: March 9, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Reinfection; Bacteremia; Recurrence; Enterobacteriaceae; Bloodstream
• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Infections; Communicable Diseases; Enterobacteriaceae Infections; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: SHORTEN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonimized data for primary and secondary variables is planned to be shared with all the participants within 6 months of data completion.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No