Optimal Antibiotics for Operated Diabetic Foot Infections

Optimization of the Surgical and Medical Management of Diabetic Foot Infections

Diabetic foot problems, especially infections (DFI), require multiple resources including iterative surgeries and amputations, long-lasting antibiotic therapies, education, off-loading and eventually revascularization and appropriate foot-ware. Treatment is complicated, multidisciplinary, and marked with a high risk of recurrences.

This is a retrospective and prospective cohort with side studies of pathologies and academic research questions that cannot be separated from each other.

The investigators establish a retro-and prospective cohort of diabetic foot problems (ambulatory and hospitalized patients) and perform side studies to reduce the incidence of complications, and to reduce recurrences of DFI, cost and adverse events related to therapies.

Cohort: Prospective and retrospective cohort of all diabetic foot problems with emphasis on surgical and infectious variables.

Trial 1 (Randomized trial on residual infection after amputation):

Determination of the level of amputation per MRI followed by a randomization concerning the duration of post-amputation systemic antibiotic therapy, if there is residual bone infection.

Trial 2 (Randomized trial on infection without amputation):

Determination of the duration of systemic antibiotic therapy in diabetic foot infections without Amputation of the infection.

Study Overview

• Status: Recruiting
• Conditions: Surgical Wound; Infection; Antibiotic Side Effect; Diabetic Foot Infection
• Intervention / Treatment: Procedure: Antibiotic therapy

Detailed Description

Trial 1: At enrollment (Day 1), the investigator will prescribe empiric antibiotic treatment based on instructions provided in the protocol and determine the most appropriate route of administration (oral or IV) according to the patient's condition. Patients will be randomized in the ratio 1:1 between 1 versus 4 days for post-amputation soft tissue infections; and between 1 versus 3 weeks if there is microbiologically proven residual bone infection/contamination in the proximal stump samples of the residual bone.

Trial 2: At enrollment (Day 1), the investigator will prescribe empiric antibiotic treatment based on instructions provided in the protocol and determine the most appropriate route of administration (oral or IV) according to the patient's condition. Patients will be randomized in the ratio 1:1 between 10 versus 20 days for post-debridement soft tissue infections; and between 3 versus 6 weeks for diabetic foot osteomyelitis post.-debridement (without amputation).

• Study Type: Interventional
• Enrollment (Anticipated): 436
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ilker Uckay, PD MD; Phone Number: +41443863705; Email: ilker.uckay@balgrist.ch
• Study Contact Backup: Name: Felix Waibel, MD; Phone Number: +41443865759; Email: felix.waibel@balgrist.ch

Study Locations

• Switzerland
  • Zurich
    • Zürich, Zurich, Switzerland, 8008
      • Recruiting
      • Balgrist University Hospital
      • Contact: Ilker Uçkay, PD, MD; Phone Number: +41 44 386 37 05; Email: ilker.uckay@balgrist.ch
      • Contact: Felix Waibel, MD; Phone Number: +41 44 386 57 59; Email: felix.waibel@balgrist.ch
      • Sub-Investigator: Martin C Berli, MD
      • Sub-Investigator: Madlaina Schöni, MD
      • Sub-Investigator: Jan Burkhard, MD
      • Sub-Investigator: Dominique Holy, MD
      • Sub-Investigator: Sabrina Catanzaro, RN
      • Sub-Investigator: Kati Sairanen, RN
      • Sub-Investigator: Tanja Huber, Pharm D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Diabetic foot infections or ischemia/necrosis with surgical amputation/disarticulation level in vicinity of MRI signs of infection
• At least two months of follow-up from hospitalization
• Patient signing to participate, including acceptance of local wound care, -off-loading and arterial re-vascularization (if clinically indicated).

Exclusion Criteria:

• At least 5 cm of distance between amputation level and infection.
• Any concomitant infection requiring more than 5 days of systemic antibiotic therapy
• Eventual osteosynthesis material not removed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1. Trial (Amputation) Soft tissue - short antibiotic arm; The intervention group consists of 1 day of postoperative antibiotic therapy for eventual residual soft tissue infection after amputation.	Procedure: Antibiotic therapy; Postoperative randomizations regarding the duration of systemic antibiotics
Active Comparator: 1. Trial (Amputation) Soft tissue - long antibiotic arm; The control group consists of 4 days duration of postoperative antibiotic therapy for eventual residual soft tissue infection after amputation.	Procedure: Antibiotic therapy; Postoperative randomizations regarding the duration of systemic antibiotics
Experimental: 1. Trial (Amputation) Bone - short antibiotic arm; The intervention group consists of 1 week of postoperative antibiotic therapy for eventual residual bone infection / contamination in the proximal bone stump after amputation.	Procedure: Antibiotic therapy; Postoperative randomizations regarding the duration of systemic antibiotics
Active Comparator: 1. Trial (Amputation) Bone - long antibiotic arm; The intervention group consists of 3 weeks of postoperative antibiotic therapy for eventual residual bone infection / contamination in the proximal bone stump after amputation.	Procedure: Antibiotic therapy; Postoperative randomizations regarding the duration of systemic antibiotics
Experimental: 2.Trial (soft tissue infection) - short antibiotic arm; The intervention group consists of 10 days of post-debridement antibiotic therapy for non-amputated diabetic foot soft tissue infection.	Procedure: Antibiotic therapy; Postoperative randomizations regarding the duration of systemic antibiotics
Active Comparator: 2. Trial (soft tissue infection) - long antibiotic arm; The control group consists of 20 days of post-debridement antibiotic therapy for non-amputated diabetic foot soft tissue infection.	Procedure: Antibiotic therapy; Postoperative randomizations regarding the duration of systemic antibiotics
Experimental: 2. Trial (osteomyelitis) - short antibiotic arm; The intervention group consists of 3 weeks of post-debridement antibiotic therapy for non-amputated diabetic foot osteomyelitis.	Procedure: Antibiotic therapy; Postoperative randomizations regarding the duration of systemic antibiotics
Active Comparator: 2. Trial (osteomyelitis) - long antibiotic arm; The control group consists of 6 weeks of post-debridement antibiotic therapy for non-amputated diabetic foot osteomyelitis.	Procedure: Antibiotic therapy; Postoperative randomizations regarding the duration of systemic antibiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with a clinical and microbiological remission of treated infection at 2 months	Remission is the absence of any anamnesis or clinics for persistent or recurrent infection	Through study completion, at 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anatomical Amputation Level Determination by MRI	Evaluation of the accuracy of the extension of infection. Surgical decision for amputation level per magnetic resonance imaging when compared to microbiology, histology and intraoperative assessment.	At study entry, Day O
Rates of adverse events of antibiotic therapy	Outcome of antibiotic-related adverse events	Through study completion, at 2 months
Duration of wound healing time	Evolution of wound size under therapy and off-loading over time. Wound Score.	Through study completion, at 2 months
Numbers of Cost and resource reductions	Overall hospitalization and treatment costs; in Swiss Francs	Through study completion, at 2 months
Scales of Patient's satisfaction	Questionnaires and Scores (e.g. AOFAS Score) ranging from 0 to 1. Alternatively, a home made Likert Scale ranging from 0 to 7 Points will be used.	Through study completion, at 2 months
Statistical evaluation of risk factors for failure of remission	Multivariate Cox Regression analyses	2 years

Collaborators and Investigators

• Sponsor: Balgrist University Hospital
• Investigators: Study Director: Ilker Uçkay, PD MD, Balgrist University Hospital, Zürich, Switzerland

Publications and helpful links

General Publications

• Uckay I, Jornayvaz FR, Lebowitz D, Gastaldi G, Gariani K, Lipsky BA. An Overview on Diabetic Foot Infections, including Issues Related to Associated Pain, Hyperglycemia and Limb Ischemia. Curr Pharm Des. 2018;24(12):1243-1254. doi: 10.2174/1381612824666180302145754.
• Coster MC, Rosengren BE, Bremander A, Brudin L, Karlsson MK. Comparison of the Self-reported Foot and Ankle Score (SEFAS) and the American Orthopedic Foot and Ankle Society Score (AOFAS). Foot Ankle Int. 2014 Oct;35(10):1031-6. doi: 10.1177/1071100714543647. Epub 2014 Jul 11.
• Rossel A, Lebowitz D, Gariani K, Abbas M, Kressmann B, Assal M, Tscholl P, Stafylakis D, Uckay I. Stopping antibiotics after surgical amputation in diabetic foot and ankle infections-A daily practice cohort. Endocrinol Diabetes Metab. 2019 Feb 6;2(2):e00059. doi: 10.1002/edm2.59. eCollection 2019 Apr.
• Uckay I, Berli M, Sendi P, Lipsky BA. Principles and practice of antibiotic stewardship in the management of diabetic foot infections. Curr Opin Infect Dis. 2019 Apr;32(2):95-101. doi: 10.1097/QCO.0000000000000530.
• Gariani K, Lebowitz D, von Dach E, Kressmann B, Lipsky BA, Uckay I. Remission in diabetic foot infections: Duration of antibiotic therapy and other possible associated factors. Diabetes Obes Metab. 2019 Feb;21(2):244-251. doi: 10.1111/dom.13507. Epub 2018 Sep 21.
• Waibel F, Berli M, Catanzaro S, Sairanen K, Schoni M, Boni T, Burkhard J, Holy D, Huber T, Bertram M, Laubli K, Frustaci D, Rosskopf A, Botter S, Uckay I. Optimization of the antibiotic management of diabetic foot infections: protocol for two randomized controlled trials. Trials. 2020 Jan 8;21(1):54. doi: 10.1186/s13063-019-4006-z.

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2019
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: August 5, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (Actual): September 9, 2019

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: diabetic foot; osteomyelitis; amputation; antibiotics
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Wounds and Injuries; Endocrine System Diseases; Disease Attributes; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Ulcer; Diabetic Foot; Infections; Communicable Diseases; Surgical Wound; Focal Infection; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: DFI_Cohort

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: not yet determined in detail
• IPD Sharing Time Frame: In 2022
• IPD Sharing Access Criteria: Upon reasonable request upon the contact authors
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No