NCT03560232

Brief Summary

To demonstrate noninferiority of three different empiric antimicrobial regimens compared to the traditional antimicrobial regimen for the management of grade III open fractures as well as evaluate outcomes among these groups.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
17

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Jul 2018

Geographic Reach
1 country

2 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 6, 2018

Completed
12 days until next milestone

First Posted

Study publicly available on registry

June 18, 2018

Completed
21 days until next milestone

Study Start

First participant enrolled

July 9, 2018

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 19, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 19, 2020

Completed
Last Updated

September 11, 2020

Status Verified

September 1, 2020

Enrollment Period

1.6 years

First QC Date

June 6, 2018

Last Update Submit

September 9, 2020

Conditions

Open FracturePost-Op Wound Infection

Keywords

Open FractureWound InfectionAntimicrobial ProphylaxisCefazolinGentamicinCeftriaxoneAmpicillin/SulbactamClindamycinPiperacillin/tazobactam

Outcome Measures

Primary Outcomes (1)

  • Post-surgical site wound infections

    The primary outcome for this study is the number of post-surgical site wound infections, defined as initiation of antibiotics for surgical-site infection and/or need for surgical debridement of site. The acceptable infection rate per Trauma Practice Management Guidelines states a rate less than 20%.

    1 year

Secondary Outcomes (3)

  • Incidence of acute kidney injury

    Hospital admission

  • Average cost of antibiotic therapy per patient

    Hospital admission

  • Time to antibiotic therapy

    Hospital admission

Study Arms (5)

Cefazolin + Gentamicin

ACTIVE COMPARATOR

\[Cefazolin\] Initial dose: * Cefazolin 2g IV x1 dose (patient weight \< 120kg) * Cefazolin 3g IV x1 dose (patient weight \>/= 120kg) Subsequent dose: * Cefazolin 2g IV every 8 hrs (CrCl \>/= 40 mL/min) * Cefazolin 2g IV every 12 hrs (CrCl 20-39 mL/min) * Cefazolin 2g IV every 24 hrs (CrCl \< 20 mL/min) Duration: * 24 hrs post-op after soft tissue coverage or total of 72 hrs, whichever comes first \[Gentamicin\] Initial dose: * If Patient age \</= 80 years old: 5 mg/kg adjusted body weight x1 dose (Max dose 500 mg) * If Patient age \>80 years old: 3 mg/kg adjusted body weight x1 dose (Max dose 300 mg) Subsequent dose: * Pharmacy Consult to dose gentamicin Duration: * 24 hrs post-op after soft tissue coverage or total of 72 hrs, whichever comes first

Drug: Cefazolin + Gentamicin

Ceftriaxone

ACTIVE COMPARATOR

Initial dose: * Ceftriaxone 2g IV x1 dose Subsequent dose: * Ceftriaxone 2g IV every 24 hours Duration: * One dose post-op after soft tissue coverage or total of 72 hours, whichever comes first

Drug: Ceftriaxone

Ampicillin/Sulbactam

ACTIVE COMPARATOR

Initial dose: * Ampicillin/Sulbactam 3g IV x1 dose Subsequent dose: * Ampicillin/Sulbactam 3g IV every 6 hours (CrCl \>/= 30 mL/min) * Ampicillin/Sulbactam 3g IV every 12 hours (CrCl 15-29 mL/min) * Ampicillin/Sulbactam 3g IV every 24 hours (CrCl \<15 mL/min) Duration: * 24 hours post-op after soft tissue coverage or total of 72 hours, whichever comes first

Drug: Ampicillin/sulbactam

Piperacillin/Tazobactam

ACTIVE COMPARATOR

Initial dose: * Piperacillin/Tazobactam 4.5g IV x1 dose over 30 minutes Subsequent dose: * Piperacillin/Tazobactam 3.375g IV every 8 hours over 4 hours (CrCl \>/= 20 mL/min) * Piperacillin/Tazobactam 3.375g IV every 12 hours over 4 hours (CrCl \< 20 mL/min) Duration: * 24 hours post-op after soft tissue coverage or total of 72 hours, whichever comes first

Drug: Piperacillin/tazobactam

Clindamycin + Gentamicin

OTHER

Patients with known Penicillin allergy will receive: \[Clindamycin\] Initial dose: * Clindamycin 900mg IV x1 dose Subsequent dose: * Clindamycin 600mg IV every 8 hours Duration: * 24 hours post-op after soft tissue coverage or total of 72 hours, whichever comes first \[Gentamicin\] Initial dose: * If Patient age \</= 80 years old: 5 mg/kg adjusted body weight x1 dose (Max dose 500 mg) * If Patient age \>80 years old: 3 mg/kg adjusted body weight x1 dose (Max dose 300 mg) Subsequent dose: * Pharmacy Consult to dose gentamicin Duration: * 24 hours post-op after soft tissue coverage or total of 72 hours, whichever comes first

Drug: Clindamycin + Gentamicin

Interventions

CeftriaxoneDRUG

See arm description

Also known as: Rocephin
Ceftriaxone
Ampicillin/sulbactamDRUG

See arm description

Also known as: Unasyn
Ampicillin/Sulbactam
Piperacillin/tazobactamDRUG

See arm description

Also known as: Zosyn
Piperacillin/Tazobactam
Cefazolin + GentamicinDRUG

See arm description

Also known as: Ancef + Garamycin
Cefazolin + Gentamicin
Clindamycin + GentamicinDRUG

See arm description

Also known as: Cleocin + Garamycin
Clindamycin + Gentamicin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age great than/equal to 18 years
  • Diagnosis of Grade III open fracture

You may not qualify if:

  • Water-borne injury
  • Farm-related injury

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

St. Joseph Warren Hospital

Warren, Ohio, 44484, United States

Location

St. Elizabeth Youngstown Hospital

Youngstown, Ohio, 44501, United States

Location

Related Publications (6)

  • Gustilo RB, Mendoza RM, Williams DN. Problems in the management of type III (severe) open fractures: a new classification of type III open fractures. J Trauma. 1984 Aug;24(8):742-6. doi: 10.1097/00005373-198408000-00009.

    PMID: 6471139BACKGROUND

  • Hoff WS, Bonadies JA, Cachecho R, Dorlac WC. East Practice Management Guidelines Work Group: update to practice management guidelines for prophylactic antibiotic use in open fractures. J Trauma. 2011 Mar;70(3):751-4. doi: 10.1097/TA.0b013e31820930e5. No abstract available.

    PMID: 21610369BACKGROUND

  • Lack WD, Karunakar MA, Angerame MR, Seymour RB, Sims S, Kellam JF, Bosse MJ. Type III open tibia fractures: immediate antibiotic prophylaxis minimizes infection. J Orthop Trauma. 2015 Jan;29(1):1-6. doi: 10.1097/BOT.0000000000000262.

    PMID: 25526095BACKGROUND

  • Otchwemah R, Grams V, Tjardes T, Shafizadeh S, Bathis H, Maegele M, Messler S, Bouillon B, Probst C. Bacterial contamination of open fractures - pathogens, antibiotic resistances and therapeutic regimes in four hospitals of the trauma network Cologne, Germany. Injury. 2015 Oct;46 Suppl 4:S104-8. doi: 10.1016/S0020-1383(15)30027-9.

    PMID: 26542854BACKGROUND

  • Rodriguez L, Jung HS, Goulet JA, Cicalo A, Machado-Aranda DA, Napolitano LM. Evidence-based protocol for prophylactic antibiotics in open fractures: improved antibiotic stewardship with no increase in infection rates. J Trauma Acute Care Surg. 2014 Sep;77(3):400-7; discussion 407-8; quiz 524. doi: 10.1097/TA.0000000000000398.

    PMID: 25159242BACKGROUND

  • Lenarz CJ, Watson JT, Moed BR, Israel H, Mullen JD, Macdonald JB. Timing of wound closure in open fractures based on cultures obtained after debridement. J Bone Joint Surg Am. 2010 Aug 18;92(10):1921-6. doi: 10.2106/JBJS.I.00547. Epub 2010 Jul 21.

    PMID: 20660225BACKGROUND

MeSH Terms

Conditions

Fractures, OpenSurgical Wound InfectionWound Infection

Interventions

CeftriaxonesultamicillinPiperacillin, Tazobactam Drug CombinationCefazolinGentamicinsClindamycin

Condition Hierarchy (Ancestors)

Fractures, BoneWounds and InjuriesInfectionsPostoperative ComplicationsPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

CefotaximeCephacetrileCephalosporinsbeta-LactamsLactamsAmidesOrganic ChemicalsThiazinesSulfur CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsTazobactamPenicillanic AcidPenicillinsPiperacillinAmpicillinPenicillin GSulfonesDrug CombinationsPharmaceutical PreparationsAminoglycosidesGlycosidesCarbohydratesLincomycinLincosamidesPyrrolidinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Natalie I Rine, PharmD

    MercyHealth Youngstown

    STUDY CHAIR

  • Paul T Miller, PharmD

    MercyHealth Youngstown

    STUDY CHAIR

  • Tyson T Schrickel, MD

    MercyHealth Youngstown

    STUDY CHAIR

  • Stuart Drew, DO

    MercyHealth Youngstown

    STUDY CHAIR

  • David J Gemmel, PhD

    MercyHealth Youngstown

    STUDY CHAIR

  • Chad W Donley, MD

    MercyHealth Youngstown

    PRINCIPAL INVESTIGATOR

  • Allison R Lauver, PharmD

    MercyHealth Youngstown

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: Randomized, open-label
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 6, 2018

First Posted

June 18, 2018

Study Start

July 9, 2018

Primary Completion

February 19, 2020

Study Completion

February 19, 2020

Last Updated

September 11, 2020

Record last verified: 2020-09

Data Sharing

IPD Sharing
Will not share

Locations

US(2)