Daptomycin as Adjunctive Therapy for Staphylococcus Aureus Bacteremia (DASH)

The purpose of our study is to examine the effects of a second antibiotic, daptomycin, in combination with a beta lactam antibiotic on treating bloodstream infection caused by methicillin-susceptible S. aureus.

Study Overview

• Status: Completed
• Conditions: Bacteremia; Methicillin Susceptible Staphylococcus Aureus Septicemia
• Intervention / Treatment: Other: Placebo; Drug: Daptomycin

Detailed Description

When patients have a blood infection with methicillin-susceptible S. aureus, they will all be treated with the usual standard of care, including abeta-lactam antibiotic, have their blood tested daily for the presence of the infection until they test negative, as well as an ultrasound of the heart to rule out an infection of the heart valves, as well as have any catheters removed (if possible) to ensure adequate control of the infection.

This study involves adding a second antibiotic, daptomycin, to the treatment regimen of half of the patients enrolled in this study. Daptomycin is approved by Health Canada for treating blood infections due to Staphylococcus aureus. It is currently not used in combination with a beta-lactam for these infections because there is insufficient evidence of benefit to justify the cost.

The study participants will receive an additional daily iv therapy which will consist of either daptomycin or a placebo for a total of five days while admitted to the hospital. During this time, the participants will continue to have their blood drawn to assess for the presence of bacteria. The participants' liver and muscle enzymes will also be measured on the first and fifth day of therapy to test for potential side effects of the daptomycin.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A3J1
      • McGill University Health Centre (Royal Victoria Hospital, Montreal Neurological Hospital, and Montreal General Hospital)

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:

• Patient has a methicillin susceptible Staphylococcus aureus bacteremia.

Exclusion Criteria:

• Underlying terminal illness
• Significant contraindication to beta-lactam therapy (i.e. severe allergy, severe adverse drug reaction)
• Expected death before 5 days
• Microbiologically confirmed need for concomitant VANCOMYCIN or DAPTOMYCIN

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 51 patients receiving a daily placebo infusion for five days on top of standard of care treatment for methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia	Other: Placebo; Placebo
Experimental: Daptomycin; 51 patients receiving daily daptomycin infusion for five days on top of standard of care treatment for MSSA bacteremia	Drug: Daptomycin; Adjuvant therapy for up to five days; Other Names: Cubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood culture clearance	Time between first positive and first negative blood culture	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Death from all causes (yes/no)	30 days
Adverse Reactions	Daptomycin adverse reactions	5 days
Intensive care admission	Admission to the intensive care unit (yes/no)	30 days
Metastatic infection	The development of a new deep seated infection (e.g. osteomyelitis, abscess, endocarditis) not present at time of initial bacteremia	30 days
Recurrent infection	The presence of a new positive blood culture occurring after the first negative culture and within 30 days of the initial positive	30 days

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Todd C Lee, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

General Publications

• Cheng MP, Lawandi A, Butler-Laporte G, De l'Etoile-Morel S, Paquette K, Lee TC. Adjunctive Daptomycin in the Treatment of Methicillin-susceptible Staphylococcus aureus Bacteremia: A Randomized, Controlled Trial. Clin Infect Dis. 2021 May 4;72(9):e196-e203. doi: 10.1093/cid/ciaa1000.
• Cheng MP, Lawandi A, Butler-Laporte G, Paquette K, Lee TC. Daptomycin versus placebo as an adjunct to beta-lactam therapy in the treatment of Staphylococcus aureus bacteremia: study protocol for a randomized controlled trial. Trials. 2018 May 29;19(1):297. doi: 10.1186/s13063-018-2668-6.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: November 21, 2016
• First Submitted That Met QC Criteria: November 23, 2016
• First Posted (Estimate): November 25, 2016

Study Record Updates

• Last Update Posted (Actual): September 22, 2020
• Last Update Submitted That Met QC Criteria: September 18, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Bacteremia; Staphylococcus aureus; Daptomycin
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Sepsis; Bacteremia; Staphylococcal Infections; Anti-Infective Agents; Anti-Bacterial Agents; Daptomycin
• Other Study ID Numbers: 2017-2666

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We will make this available under the right conditions including the appropriate data sharing agreements and ethics applications under Quebec law.