Seven Versus Fourteen Days of Treatment in Uncomplicated Staphylococcus Aureus Bacteremia

NCT03514446 | Unknown Phase 4 FDA Drug

• 2 other identifiers: H-170274142017-003529-13
• Study Type: interventional
• Target: 284
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: Staphylococcus aureus bacteremia (SAB) plays an important role in long-course antibiotic therapy. Current international guidelines recommend fourteen days of intravenous antibiotic treatment for SAB in order to minimize risks of secondary deep infections and complications. However, patients with simple SAB are known to have a low risk of complications. Reducing treatment length in uncomplicated SAB would reduce the total consumption of antibiotics, adverse events and duration of hospital admission. SAB7 seeks to determine if seven days of antibiotic treatment in patients with uncomplicated SAB is non-inferior to fourteen days of treatment. Method: The study is designed as a randomized, non-blinded, non-inferiority interventional study. Primary measure of outcome will be failure to treatment or recurrence of SAB twelve weeks after termination of antibiotic treatment. As a measure of secondary outcome the prevalence of severe adverse effects will be evaluated, in particular secondary infection with Clostridium difficile, mortality as well as public health related costs. Patients identified with uncomplicated SAB, are randomized 1:1 in two parallel arms to seven or fourteen days of antimicrobial treatment, respectively. Endpoints will be tested with a statistical non-inferiority margin of 10%. Conclusion: SAB 7 will determine if seven days of antibiotic treatment in patients with uncomplicated SAB is sufficient and safe, potentially modifying current treatment recommendations.

Conditions

Staphylococcus Aureus Bacteremia

Outcome Measures

Primary Outcomes (1)

• 90-day survival without clinical or microbiological failure to treatment or relapse

  up to 90 days

Secondary Outcomes (9)

• Microbiologically failure to treatment

  less than 7 days after treatment termination

• Microbiologically relapse

  more than 7 days after treatment termination

• Clinical failure to treatment or relapse

  Up to day 90

• Mortality

  Days 14, 28, 90 and 180

• Severe adverse events

  Up to 26 weeks

Study Arms (2)

Antibiotic therapy duration for 7 days

EXPERIMENTAL

Drug: Antibiotic therapy duration for 7 days

Antibiotic therapy duration for 14 days

NO INTERVENTION

Interventions

Antibiotic therapy duration for 7 days DRUG

Antibiotic therapy for seven days

Antibiotic therapy duration for 7 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Blood culture positive for Staphylococcus aureus
• Antibiotic treatment with antimicrobial activity to S. aureus administrated within 12 hours of the first positive blood culture
• Temperature \< 37,5 degrees celsius at randomization
• S. aureus negative follow-up blood culture obtained 48-96 hours after microbiological verified SAB.
• Patients written consent obtained

You may not qualify if:

• Persistence of S. aureus bacteremia before randomization (S. aureus positive follow-up blood culture obtained 48-96 hours of the first positive blood culture)
• Polymicrobial infection
• Antibiotic treatment whit no antimicrobial activity to S. aureus administrated more than 12 hours of the first positive blood culture
• Endocarditis or other intracardiac infection demonstrated with transthoracic or transesophageal echocardiography
• Previous history of endocarditis
• Pacemaker or other intracardiac implant
• Failure to remove a likely focus of infection, such as central venous catheter within 72 hours of the first positive blood culture.
• Prosthetics in joints and bones or vascular grafts
• Pneumonia or infection involving bone or joints
• Previously bone/join infection
• S. aureus infection within the last 90 days
• Pregnancy or breastfeeding
• Neutropenia (blood neutrophils \< 1,0 x 109/l)
• Untreated cancer
• Chemotherapy within 90 days.

Sponsors & Collaborators

• Thomas Benfield: lead

Study Sites (1)

Hvidovre Hospital

Hvidovre, Copenhagen, 2650, Denmark

RECRUITING

Related Publications (15)

• Banaei N, Anikst V, Schroeder LF. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015 Jun 11;372(24):2368-9. doi: 10.1056/NEJMc1505190. No abstract available.

  PMID: 26061852 BACKGROUND

• Kaasch AJ, Fatkenheuer G, Prinz-Langenohl R, Paulus U, Hellmich M, Weiss V, Jung N, Rieg S, Kern WV, Seifert H; SABATO trial group (with linked authorship to the individuals in the Acknowledgements section). Early oral switch therapy in low-risk Staphylococcus aureus bloodstream infection (SABATO): study protocol for a randomized controlled trial. Trials. 2015 Oct 9;16:450. doi: 10.1186/s13063-015-0973-x.

  PMID: 26452342 BACKGROUND

• Thwaites GE, Edgeworth JD, Gkrania-Klotsas E, Kirby A, Tilley R, Torok ME, Walker S, Wertheim HF, Wilson P, Llewelyn MJ; UK Clinical Infection Research Group. Clinical management of Staphylococcus aureus bacteraemia. Lancet Infect Dis. 2011 Mar;11(3):208-22. doi: 10.1016/S1473-3099(10)70285-1.

  PMID: 21371655 BACKGROUND

• Blyth CC, Darragh H, Whelan A, O'Shea JP, Beaman MH, McCarthy JS. Evaluation of clinical guidelines for the management of Staphylococcus aureus bacteraemia. Intern Med J. 2002 May-Jun;32(5-6):224-32. doi: 10.1046/j.1445-5994.2001.00205.x.

  PMID: 12036220 BACKGROUND

• Benfield T, Espersen F, Frimodt-Moller N, Jensen AG, Larsen AR, Pallesen LV, Skov R, Westh H, Skinhoj P. Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteraemia between 1981 and 2000. Clin Microbiol Infect. 2007 Mar;13(3):257-63. doi: 10.1111/j.1469-0691.2006.01589.x.

  PMID: 17391379 BACKGROUND

• Zeylemaker MM, Jaspers CA, van Kraaij MG, Visser MR, Hoepelman IM. Long-term infectious complications and their relation to treatment duration in catheter-related Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis. 2001 Jun;20(6):380-4. doi: 10.1007/pl00011278.

  PMID: 11476436 BACKGROUND

• Raad II, Sabbagh MF. Optimal duration of therapy for catheter-related Staphylococcus aureus bacteremia: a study of 55 cases and review. Clin Infect Dis. 1992 Jan;14(1):75-82. doi: 10.1093/clinids/14.1.75.

  PMID: 1571466 BACKGROUND

• Fowler VG Jr, Sanders LL, Sexton DJ, Kong L, Marr KA, Gopal AK, Gottlieb G, McClelland RS, Corey GR. Outcome of Staphylococcus aureus bacteremia according to compliance with recommendations of infectious diseases specialists: experience with 244 patients. Clin Infect Dis. 1998 Sep;27(3):478-86. doi: 10.1086/514686.

  PMID: 9770144 BACKGROUND

• Mylotte JM, McDermott C, Spooner JA. Prospective study of 114 consecutive episodes of Staphylococcus aureus bacteremia. Rev Infect Dis. 1987 Sep-Oct;9(5):891-907. doi: 10.1093/clinids/9.5.891.

  PMID: 3317734 BACKGROUND

• Ehni WF, Reller LB. Short-course therapy for catheter-associated Staphylococcus aureus bacteremia. Arch Intern Med. 1989 Mar;149(3):533-6.

  PMID: 2919931 BACKGROUND

• Larsen AR, Stegger M, Sorum M. spa typing directly from a mecA, spa and pvl multiplex PCR assay-a cost-effective improvement for methicillin-resistant Staphylococcus aureus surveillance. Clin Microbiol Infect. 2008 Jun;14(6):611-4. doi: 10.1111/j.1469-0691.2008.01995.x. Epub 2008 Apr 3.

  PMID: 18393997 BACKGROUND

• Mejer N, Westh H, Schonheyder HC, Jensen AG, Larsen AR, Skov R, Benfield T; Danish Staphylococcal Bacteraemia Study Group. Stable incidence and continued improvement in short term mortality of Staphylococcus aureus bacteraemia between 1995 and 2008. BMC Infect Dis. 2012 Oct 17;12:260. doi: 10.1186/1471-2334-12-260.

  PMID: 23075215 BACKGROUND

• Mylotte JM, McDermott C. Staphylococcus aureus bacteremia caused by infected intravenous catheters. Am J Infect Control. 1987 Feb;15(1):1-6. doi: 10.1016/0196-6553(87)90069-1.

  PMID: 3645972 BACKGROUND

• Iannini PB, Crossley K. Therapy of Staphylococcus aureus bacteremia associated with a removable focus of infection. Ann Intern Med. 1976 May;84(5):558-60. doi: 10.7326/0003-4819-84-5-558.

  PMID: 1275357 BACKGROUND

• Jensen AG, Wachmann CH, Espersen F, Scheibel J, Skinhoj P, Frimodt-Moller N. Treatment and outcome of Staphylococcus aureus bacteremia: a prospective study of 278 cases. Arch Intern Med. 2002 Jan 14;162(1):25-32. doi: 10.1001/archinte.162.1.25.

  PMID: 11784216 BACKGROUND

Related Links

• Related Info

Central Study Contacts

Louise Thorlacius-Ussing, MD

CONTACT

+45 26457710; louise.thorlacius-ussing@regionh.dk

Thomas Benfield, MD, DMSc

CONTACT

Thomas.Lars.Benfield@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: November 10, 2017
• First Posted: May 2, 2018
• Study Start: June 1, 2018
• Primary Completion: May 1, 2021
• Study Completion: November 1, 2021
• Last Updated: October 19, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)