Randomized Control Trial of Meropenem versus Piperacillin-Tazobactam for definitive treatment of bloodstream infections due to ceftriaxone non-susceptible Escherichia Coli and Klebsiella species.

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12615000403538
• Date of registration: 30/04/2015
• Prospective Registration: No
• Primary sponsor: Australasian Society of Infectious Diseases Clinical Research Network
• Public title: Randomized Control Trial of Meropenem versus Piperacillin-Tazobactam for definitive treatment of bloodstream infections due to ceftriaxone non-susceptible Escherichia Coli and Klebsiella species.
• Scientific title: Randomized Control Trial of Meropenem versus Piperacillin-Tazobactam on mortality and clinial response in patients with bloodstream infections due to ceftriaxone non-susceptible Escherichia Coli and Klebsiella species.
• Date of first enrolment: 16/04/2015
• Target sample size: 454
• Recruitment status: Stopped early
• URL: https://anzctr.org.au/ACTRN12615000403538.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Efficacy;
• Phase: Phase 4

Countries of recruitment

Australia, Canada, Italy, Lebanon, Malaysia, New Zealand, Saudi Arabia, Singapore, South Africa, Turkey

Contacts

• Name: Prof David L. Paterson

• Name: Prof David L. Paterson

Key inclusion & exclusion criteria

Inclusion criteria: 1. Bloodstream infection with Escherichia coli or Klebsiella spp., as defined by at least one positive blood culture from a peripheral blood draw.
2. Bacteria confirmed as ceftriaxone non-susceptible, Piperacillin-Tazobactam susceptible and Meropenem susceptible by use of EUCAST definitions (www.eucast.org).
3. No more than 72 hours since the first positive blood culture was collected for this infection.
4. Patient or their ethics committee approved proxy able to give written informed consent.
Exclusion criteria: 1. Patient not expected to survive more than 4 days.
2. Patient allergic to a penicillin or a carbapenem.
3. Patient with significant polymicrobial bacteraemia (that is, a Gram positive skin containment in one set of blood cultures is not regarded as significant polymicrobial bacteraemia).
4. Treatment is not with the intent to cure the infection (that is, palliative care is an exclusion).

Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Escherichia Coli blood infection ;Klebsiella species blood infection;
Escherichia Coli blood infection
Klebsiella species blood infection

Infection - Other infectious diseases

Intervention(s)

Recruited participants will randomly be assigned to either receive the study drugs of Meropenem or Piperacillin-Tazobactam in a 1:1 ratio according to a randomisation list prepared in advance. The intervention treatment for this study is the administration of the drug Piperacillin-Tazobactam 4.5 grams administered every 6 hours intravenously over a 30 minute period. The duration of treatment with this drug will be for a minimum of 4 days and a maximum of 14 days. The duration of the therapy will be determined by the treating clinician.

Primary Outcome(s)

1. The primary outcome for the trial is the occurence and confirmation of mortality at 30 days after the first positive blood culture.[30 days post first positive blood culture.]

Secondary Outcome(s)

1. Time to clinical and microbiologic resolution.[Number of days from initiation of study drug to resolution of SIRS PLUS sterilisation of blood cultures.]

3. Microbiologic resolution of infection.[Sterility of blood cultures on 3rd day post initial recruitment.]

4. Microbiologic relapse.[Growth of the same organism as in the original blood culture after the end of the period of study drug administration, before 30 days after the first positive blood culture was drawn.]

2. Clinical and microbiologic success.[Survival at day four after the initation of study drug PLUS resolution of SIRS on or before day four PLUS sterilisation of blood cultures on or before day four.]

Secondary ID(s)

Nil

Source(s) of Monetary Support

Australian Society for Infectious Diseases

Australian Society for Antimicrobials

Secondary Sponsor(s)

University of Queensland Centre for Clinical Research

Ethics review

Status: Approved
Approval date:
Contact:

Royal Brisbane & Women's Hospital Human Research Ethics Committee