Impact of Antibiotic Treatment Following Implantation of Cardiac Electronic Device on Patient's Outcome

• ClinicalTrials.gov Identifier: NCT03148444
• Recruitment Status: Unknown
• First Posted: May 11, 2017
• Last Update Posted: May 11, 2017
• Sponsor: Kaplan Medical Center
• Information provided by (Responsible Party): Moshe Swissa, Kaplan Medical Center

Tracking Information

• First Submitted Date: May 9, 2017
• First Posted Date: May 11, 2017
• Last Update Posted Date: May 11, 2017
• Estimated Study Start Date: June 1, 2017
• Estimated Primary Completion Date: June 1, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 10, 2017)

• wound infection [ Time Frame: 1 year ]
  operative wound infection or infection of the device pouch
• bacteremia and vegetations [ Time Frame: 1 year ]
  bacteremia due to device infection, lead vegetation, right infective endocarditis
• re-operation [ Time Frame: 1 year ]
  re-operation due to infective complications

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: May 10, 2017)

• infection unrelated to implantation [ Time Frame: 1 year ]
  any infection (e.g. bacteremia, urinary tract infection, diarrhea) unrelated to the implantable device, whether demanding hospitalization or not
• hospitalization [ Time Frame: 1 year ]
  any hospitalization due to non-infective problems related to the implantable device
• adverse event of antibiotics [ Time Frame: 1 year ]
  any event related to adverse effect of antibiotics warranting discontinuation of the drug e.g. allergy
• death from any cause [ Time Frame: 1 year ]
  death from any cause unrelated to the problems enumerated among primary outcomes

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Impact of Antibiotic Treatment Following Implantation of Cardiac Electronic Device on Patient's Outcome
• Official Title: Impact of Antibiotic Treatment Following Implantation of Cardiac Electronic Device on Patient's Outcome

Brief Summary

Background: Infection of cardiac implantable electronic device including wound and pouch infection, bacteraemia and endocarditis is a common complication of device insertion. The role of antibiotic prophylaxis in prevention of this complication is well established. Most centres in Israel currently prescribe antibiotics about 5 days following the procedure as well, though clear clinical evidence warranting this practise is lacking. Unnecessary antibiotic treatment can lead to adverse events including allergy, undesirable effects of the antibiotics, establishment of resistance to antibiotics among bacteria and further infections with resistant strains.

Objective: The investigators hope to either establish evidence warranting use of post-procedural antibiotic treatment or refuting it.

Methods: The investigators intend to recruit about 400 patients a year into both trial group and control group. The trial group will be treated with post-procedural antibiotics during 5 days, while the control group will receive no post-procedural antibiotics. The endpoints of the study will include infections related to the implantable device and proposed adverse effects of the antibiotics. The t-test will be performed in order to evaluate whether benefit exists concerning one of the groups.

Detailed Description

The infection of cardiac implantable electronic device site (including both pocket infection and deeper infections) is a common complication of electronic device insertion. Its incidence is estimated in different series as 0.2-0.7 per 100 device-years. The risk factors that raise the incidence of this complication are in the first place lack of or inappropriate antibiotic prophylaxis and repeated or recurrent manipulations with the device. Several comorbidities such as diabetes, renal insufficiency, heart failure, malignancy, anticoagulation treatment, and, non-surprisingly glucocorticoid treatment are the remaining risk factors for the infection. It is worth mentioning that over half of all cases of infection occur during the first year past implantation.

About 75% of all device infections are caused by staphylococci (both S. aureus and coagulase negative staphylococci). The other causative organisms are streptococci, Corynebacterium species, Propionibacterium, gram-negative bacilli and fungi. Main source of infection appears to be pocket contamination by skin flora. In one study the swab specimens obtained from device pockets during the procedure rendered positive culture for coagulase-negative staphylococci in up to one half of the specimens even despite observant aseptic technique and appropriate antibiotic prophylaxis.Thus, the contamination leading to infection of the implantation site can occur during the procedure. Other possible paths for infection include erosion of the device or its leads through the skin and seeding of the device and its leads by systemic bacteremia. The treatment of this complication usually requires explantation of the infected device, intravenous antibiotic treatment and then implantation of a new device through the non-infected route.

The principal approach to prevent device infection remain aseptic technique during the procedure and appropriate antibiotic prophylaxis. Different clinical trials showed that pre-treatment of elective patients before the device implantation with anti-staphylococcal penicillins or with first generation cephalosporins results in decrease in rate of infection with odds ratio about 0.2-0.25.Therefore, current recommendation is to pre-treat patients before implantation of the device with 2-3 gram cefazolin or 1.5 gram cefuroxime, or 15 mg/kg vancomycin or clindamycin 900 mg IV within 4 hours before the procedure. Currently there is no evidence regarding adjuvant antibiotic treatment after the implantation. In the face of lack of evidence, several medical centres in Israel either non-uniformly administer different antibiotic regimens following the implantation or refrain from routinely prescribing any antibiotics to the patients following the implantation.

Objective:

The investigators suppose that non-necessary antibiotic treatment entails several adverse outcomes including direct adverse effects of the antibiotics (e.g. allergy, gastrointestinal effects, QT-prolongation), and induction of resistance to antibiotics among the patient's microflora entailing further infections with resistant bacteria (e.g. urinary tract infections, diarrhea). Therefore, an evidence either warranting use of antibiotics following the implantation of implantable electronic device or refuting it should be established.

Medications:

1. cefalexin 500 mg qid,
2. roxithromycin 150 mg bid Both medications are authorized in Israel for a variety of infections or infection prevention including prevention of implantable cardiac electronic device infection. Both medications are routinely prescribed in medical centres in Israel following implantation of cardiac electronic devices.

• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

We propose to organize a randomized open-label study in which patients undergoing de novo implantation or replacement of cardiac implantable devices (single-chamber, dual-chamber and biventricular pacemakers and defibrillators) will be randomly assigned to one of the two groups. Patients in one group will be discharged home with recommendations to take antibiotic treatment for 5 days following the procedure (cefalexin 500 mg qid, or in the presence of beta-lactam sensitivity roxythromycin 150 mg bid) while in the other group no recommendations regarding antibiotic treatment will be given. Both groups will receive antibiotic prophylaxis before the procedure according to the current recommendations. In both groups, the aseptic technique during the procedure will be observed, and proper hygienic measures past the implantation will be taken.

Masking: Double (Investigator, Outcomes Assessor)
Masking Description:

The random assignment will be performed by a researcher from the cardiologic team performing the implantation by means of choosing one of two closed envelopes. The treatment will not be placebo-controlled, and therefore the neither the patients nor the attending physicians will not be blinded to the final results of the assignment.

Primary Purpose: Prevention

Condition

• Infection, Bacterial
• Pacemaker Complication

Intervention

Drug: cefalexin 500 mg qid or roxithromycin 150 mg bid

antibiotics treatment for five days following implantation of cardiac device

Study Arms

• Experimental: Antibiotics treated
  Patients undergoing de novo implantation or replacement of cardiac implantable devices (single-chamber, dual-chamber and biventricular pacemakers and defibrillators) in our institution will be discharged home with recommendations to take antibiotic treatment for 5 days following the procedure (cefalexin 500 mg qid, or in the presence of beta-lactam sensitivity roxithromycin 150 mg bid)
  Intervention: Drug: cefalexin 500 mg qid or roxithromycin 150 mg bid
• No Intervention: without Antibiotics Treatment
  Patients undergoing de novo implantation or replacement of cardiac implantable devices (single-chamber, dual-chamber and biventricular pacemakers and defibrillators) in our institution will be discharged home with no recommendations regarding antibiotic treatment.

Publications *

• Uslan DZ, Sohail MR, St Sauver JL, Friedman PA, Hayes DL, Stoner SM, Wilson WR, Steckelberg JM, Baddour LM. Permanent pacemaker and implantable cardioverter defibrillator infection: a population-based study. Arch Intern Med. 2007 Apr 9;167(7):669-75.
• Klug D, Balde M, Pavin D, Hidden-Lucet F, Clementy J, Sadoul N, Rey JL, Lande G, Lazarus A, Victor J, Barnay C, Grandbastien B, Kacet S; PEOPLE Study Group. Risk factors related to infections of implanted pacemakers and cardioverter-defibrillators: results of a large prospective study. Circulation. 2007 Sep 18;116(12):1349-55. Epub 2007 Aug 27.
• Smith PN, Vidaillet HJ, Hayes JJ, Wethington PJ, Stahl L, Hull M, Broste SK. Infections with nonthoracotomy implantable cardioverter defibrillators: can these be prevented? Endotak Lead Clinical Investigators. Pacing Clin Electrophysiol. 1998 Jan;21(1 Pt 1):42-55.
• Da Costa A, Lelièvre H, Kirkorian G, Célard M, Chevalier P, Vandenesch F, Etienne J, Touboul P. Role of the preaxillary flora in pacemaker infections: a prospective study. Circulation. 1998 May 12;97(18):1791-5. Review.
• Da Costa A, Kirkorian G, Cucherat M, Delahaye F, Chevalier P, Cerisier A, Isaaz K, Touboul P. Antibiotic prophylaxis for permanent pacemaker implantation: a meta-analysis. Circulation. 1998 May 12;97(18):1796-801.
• de Oliveira JC, Martinelli M, Nishioka SA, Varejão T, Uipe D, Pedrosa AA, Costa R, D'Avila A, Danik SB. Efficacy of antibiotic prophylaxis before the implantation of pacemakers and cardioverter-defibrillators: results of a large, prospective, randomized, double-blinded, placebo-controlled trial. Circ Arrhythm Electrophysiol. 2009 Feb;2(1):29-34. doi: 10.1161/CIRCEP.108.795906. Epub 2009 Feb 10. Erratum in: Circ Arrhythm Electrophysiol. 2009 Feb;2(1):e1. D'Avila, Andre [added].
• Sohail MR, Uslan DZ, Khan AH, Friedman PA, Hayes DL, Wilson WR, Steckelberg JM, Stoner S, Baddour LM. Management and outcome of permanent pacemaker and implantable cardioverter-defibrillator infections. J Am Coll Cardiol. 2007 May 8;49(18):1851-9. Epub 2007 Apr 23.
• Lekkerkerker JC, van Nieuwkoop C, Trines SA, van der Bom JG, Bernards A, van de Velde ET, Bootsma M, Zeppenfeld K, Jukema JW, Borleffs JW, Schalij MJ, van Erven L. Risk factors and time delay associated with cardiac device infections: Leiden device registry. Heart. 2009 May;95(9):715-20. doi: 10.1136/hrt.2008.151985. Epub 2008 Nov 26.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: May 10, 2017): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 1, 2020
• Estimated Primary Completion Date: June 1, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• patients undergoing de novo implantation or replacement of cardiac implantable devices (single-chamber, dual-chamber and biventricular pacemakers and defibrillators) in our institution.

Exclusion Criteria:

• procedure during which, according to the opinion of the operator, the risk of the contamination would be unusually high (for ex. due to prolonged duration) so that obligatory post-operative use of antibiotics should be warranted,
• patients with any immunosuppressive condition (including cytotoxic chemotherapy, chronic use of glucocorticoids, however excluding diabetes mellitus, renal failure and heart failure);
• malignancy,
• pregnancy and breastfeeding;
• hepatic cirrhosis;
• end stage renal disease (GFR<10 mL/min);
• known allergy to both antibiotic medications used in the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT03148444
• Other Study ID Numbers: kmc 0038-16
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Moshe Swissa, Kaplan Medical Center
• Study Sponsor: Kaplan Medical Center
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Kaplan Medical Center
• Verification Date: May 2017