Seven Versus Fourteen Days of Treatment in Uncomplicated Staphylococcus Aureus Bacteremia

NCT ID: NCT03514446

Last Updated: 2020-10-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

284 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-01

Study Completion Date

2021-11-01

Brief Summary

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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.

Detailed Description

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Conditions

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Staphylococcus Aureus Bacteremia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Antibiotic therapy duration for 7 days

Group Type EXPERIMENTAL

Antibiotic therapy duration for 7 days

Intervention Type DRUG

Antibiotic therapy for seven days

Antibiotic therapy duration for 14 days

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Antibiotic therapy duration for 7 days

Antibiotic therapy for seven days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Thomas Benfield

OTHER

Sponsor Role lead

Responsible Party

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Thomas Benfield

Clinical Professor

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Hvidovre Hospital

Hvidovre, Copenhagen, Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Louise Thorlacius-Ussing, MD

Role: CONTACT

+45 26457710

Thomas Benfield, MD, DMSc

Role: CONTACT

Facility Contacts

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Louise Ussing, MD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 26061852 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26452342 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21371655 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12036220 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17391379 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11476436 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1571466 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9770144 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3317734 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 2919931 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18393997 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23075215 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3645972 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1275357 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11784216 (View on PubMed)

Related Links

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Other Identifiers

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2017-003529-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

H-17027414

Identifier Type: -

Identifier Source: org_study_id

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