Oritavancin for CIED Infections With MDR Gram-positive Cocci

NCT07013552 | Not Yet Recruiting

• 1 other identifier: KPOD.07.07-IW.07-0004/24
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The study aimed to conduct a randomized, non-inferiority controlled trial to compare the short- and medium-term efficacy and safety of two antibiotic dosage regimens in cardiac implantable electronic devices (CIED) infections with multidrug-resistant Gram-positive cocci: 1) single-dose therapy with a long-half-life antibiotic (oritavancin) vs. standard 7-14 days of therapy with a short-half-life antibiotic (vancomycin) for CIED surgical incision site or pocket infection; and 2) fractionated therapy with a long-half-life antibiotic (oritavancin) at seven-day intervals compared to standard therapy with a short-half-life antibiotic (vancomycin) fractionated in 2-3 daily doses in cases of lead-related infectious endocarditis.

Conditions

Cardiac Implantable Electronic Device Infections; Infective Endocarditis; Multidrug-resistant Bacteria Screening; Gram Positive Bacterial Infection; Antibiotic Resistant Strain; Antibiotic Therapy; Healthcare Associated Infections

Keywords

Cardiac implantable electronic device; Gram-positive cocci; Health-care associated infections; Lead-related infective endocarditis; Multidrug-resistant bacteria; Pocket infection

Outcome Measures

Primary Outcomes (2)

• Co-primary efficacy endpoint - treatment success rate

  Treatment success will be defined as obtaining a clinical response and no recurrence of infection at the same site or the site of CIED reimplantation within three months of F/U.

  3 months

• Co-primary safety endpoint - no treatment-related Serious Adverse Events

  Any adverse event classified as grade 3-5 according Health Technology Assessment report developed by the Agency for Health Technology Assessment and Tariff System (Poland) and related to using the investigational product (scores of 3-5) will be counted as a safety endpoint.

  3 months

Secondary Outcomes (6)

• Clinical response rate

  3 months

• Median time to clinical response

  3 months

• Recurrent infection rate

  3 months

• Rehospitalization rate due to recurrent infection

  3 months

• Proportion of cases in which infection worsened from superficial or local to systemic despite drug therapy

  3 months

Study Arms (2)

Patients treated with a long half-life antibiotic - oritavancin (Tenkasi)

EXPERIMENTAL

Patients with CIED infection with MDR Gram-positive cocci treated with a long half-life lipoglycopeptide antibiotic - oritavancin

Drug: Administration of a single or repeated dose of a long half-life antibiotic - oritavancin

Patients treated with a short half-life antibiotic - vancomycin (Vancomycin)

ACTIVE COMPARATOR

Patients with CIED infection with MDR Gram-positive cocci treated with a short half-life glycopeptide antibiotic - vancomycin

Drug: Administration of a repeated dose of a short half-life antibiotic - vancomycin

Interventions

Administration of a single or repeated dose of a long half-life antibiotic - oritavancin DRUG

Intravenous administration of a single or repeated dose of lipoglycopeptide antibiotic - oritavancin. In superficial ABSSSI or PI: Single dose of 1,200 mg (3 vials) administered as a 3-hour intravenous infusion in 5% glucose solution. In LRIE: First dose of 1,200 mg (3 vials) administered as a 3-hour intravenous infusion in 5% glucose solution, subsequent doses of 800 mg (2 vials) administered as a 2-3 hour intravenous infusion at 7-day intervals, to achieve the required duration of drug therapy of 2-6 weeks (counted from the day of transvenous lead extraction).

Patients treated with a long half-life antibiotic - oritavancin (Tenkasi)

Administration of a repeated dose of a short half-life antibiotic - vancomycin DRUG

Intravenous administration of repeated doses of glycopeptide antibiotic - vancomycin. Repeated doses of 15-20 mg/kg body weight every 8-12 hours administered as an hourly intravenous infusion in 0.9% sodium chloride solution, under monitoring the drug concentration in serum, for 7-10 days in ABSSSI, for 10-14 days in PI, and for 2-6 weeks in LRIE (counted from the day of transvenous lead extraction).

Patients treated with a short half-life antibiotic - vancomycin (Vancomycin)

Eligibility Criteria

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

You may qualify if:

• Completed 18 years of age
• Presence of signs and symptoms of superficial ABSSSI or PI in the form of a) redness/warmth/swelling/pain or b) separation of the edges of the surgical incision with signs of inflammation or the need for repeated surgical debridement of the wound or c) the presence of decubitus of the skin and subcutaneous tissue in area of the generator or skin abscess/erosion of the device pocket, with purulent discharge from the wound or discharge giving a positive microbial culture
• Probable/ definite diagnosis of right-sided LRIE according to modified Dukes criteria (optional criterion)
• Suspected/confirmed infection with drug-resistant Gram-positive cocci, i.e., Staphylococcus spp. (Stahphylococcus aureus or coagulase-negative staphylococci), Streptococcus spp. or Enterococcus spp. sensitive to oritavancin
• Suspected/confirmed infection with Gram-positive cocci, i.e., Staphylococcus spp., Streptococcus spp., Enterococcus spp., sensitive to vancomycin or oritavancin and beta-lactam antibiotics in patients with a history of type I anaphylaxis to penicillin.

You may not qualify if:

• Suspected/confirmed infection with Gram-positive or Gram-negative bacilli or anaerobic bacteria
• Suspected/confirmed community-acquired infection or infection with Gram-positive cocci sensitive to betalactam antibiotics, including penicillin, ampicillin, or methicillin, based on empirical data or cultures (does not apply to patients with a history of type I anaphylaxis to penicillin)
• Confirmed resistance of Gram-positive cocci, which are the etiological factor of the infection, to vancomycin and oritavancin.
• History of hypersensitivity to oritavancin or another lipoglycopeptide antibiotic (applies to the experimental group only)
• History of hypersensitivity to vancomycin or another glycopeptide antibiotics (applies to the control group only)
• No possibility of temporarily interrupting/initiating alternative therapy to intravenous infusion of unfractionated heparin
• Pregnancy or breastfeeding
• Lack of informed written consent of the patient to participate in the study

Sponsors & Collaborators

• Medical University of Silesia: lead
• Medical Research Agency, Poland: collaborator

Study Sites (1)

Department of Electrocardiology and Heart Failure, Medical University of Silesia in Katowice

Katowice, Silesian Voivodeship, 40-635, Poland

Location

Related Publications (21)

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  PMID: 38157921 BACKGROUND

• Olsen T, Jorgensen OD, Nielsen JC, Thogersen AM, Philbert BT, Johansen JB. Incidence of device-related infection in 97 750 patients: clinical data from the complete Danish device-cohort (1982-2018). Eur Heart J. 2019 Jun 14;40(23):1862-1869. doi: 10.1093/eurheartj/ehz316.

  PMID: 31155647 BACKGROUND

• Stewart CL, Turner MS, Frens JJ, Snider CB, Smith JR. Real-World Experience with Oritavancin Therapy in Invasive Gram-Positive Infections. Infect Dis Ther. 2017 Jun;6(2):277-289. doi: 10.1007/s40121-017-0156-z. Epub 2017 Apr 6.

  PMID: 28386776 BACKGROUND

• Morrisette T, Miller MA, Montague BT, Barber GR, McQueen RB, Krsak M. On- and off-label utilization of dalbavancin and oritavancin for Gram-positive infections. J Antimicrob Chemother. 2019 Aug 1;74(8):2405-2416. doi: 10.1093/jac/dkz162.

  PMID: 31322694 BACKGROUND

• Rubino CM, Bhavnani SM, Moeck G, Bellibas SE, Ambrose PG. Population pharmacokinetic analysis for a single 1,200-milligram dose of oritavancin using data from two pivotal phase 3 clinical trials. Antimicrob Agents Chemother. 2015;59(6):3365-72. doi: 10.1128/AAC.00176-15. Epub 2015 Mar 30.

  PMID: 25824211 BACKGROUND

• Carvalhaes CG, Sader HS, Streit JM, Castanheira M, Mendes RE. Activity of Oritavancin against Gram-Positive Pathogens Causing Bloodstream Infections in the United States over 10 Years: Focus on Drug-Resistant Enterococcal Subsets (2010-2019). Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0166721. doi: 10.1128/AAC.01667-21. Epub 2021 Nov 22.

  PMID: 34807761 BACKGROUND

• Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N; WHO Pathogens Priority List Working Group. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018 Mar;18(3):318-327. doi: 10.1016/S1473-3099(17)30753-3. Epub 2017 Dec 21.

  PMID: 29276051 BACKGROUND

• Lupia T, De Benedetto I, Bosio R, Shbaklo N, De Rosa FG, Corcione S. Role of Oritavancin in the Treatment of Infective Endocarditis, Catheter- or Device-Related Infections, Bloodstream Infections, and Bone and Prosthetic Joint Infections in Humans: Narrative Review and Possible Developments. Life (Basel). 2023 Apr 6;13(4):959. doi: 10.3390/life13040959.

  PMID: 37109488 BACKGROUND

• Thomas G, Henao-Martinez AF, Franco-Paredes C, Chastain DB. Treatment of osteoarticular, cardiovascular, intravascular-catheter-related and other complicated infections with dalbavancin and oritavancin: A systematic review. Int J Antimicrob Agents. 2020 Sep;56(3):106069. doi: 10.1016/j.ijantimicag.2020.106069. Epub 2020 Jun 27.

  PMID: 32603683 BACKGROUND

• Esposito S, Blasi F, Curtis N, Kaplan S, Lazzarotto T, Meschiari M, Mussini C, Peghin M, Rodrigo C, Vena A, Principi N, Bassetti M. New Antibiotics for Staphylococcus aureus Infection: An Update from the World Association of Infectious Diseases and Immunological Disorders (WAidid) and the Italian Society of Anti-Infective Therapy (SITA). Antibiotics (Basel). 2023 Apr 12;12(4):742. doi: 10.3390/antibiotics12040742.

  PMID: 37107104 BACKGROUND

• Corey GR, Arhin FF, Wikler MA, Sahm DF, Kreiswirth BN, Mediavilla JR, Good S, Fiset C, Jiang H, Moeck G, Kabler H, Green S, O'Riordan W; SOLO I, SOLO II Investigators. Pooled analysis of single-dose oritavancin in the treatment of acute bacterial skin and skin-structure infections caused by Gram-positive pathogens, including a large patient subset with methicillin-resistant Staphylococcus aureus. Int J Antimicrob Agents. 2016 Nov;48(5):528-534. doi: 10.1016/j.ijantimicag.2016.07.019. Epub 2016 Sep 13.

  PMID: 27665522 BACKGROUND

• Giske CG, Turnidge J, Canton R, Kahlmeter G; EUCAST Steering Committee. Update from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). J Clin Microbiol. 2022 Mar 16;60(3):e0027621. doi: 10.1128/JCM.00276-21. Epub 2021 Aug 4.

  PMID: 34346716 BACKGROUND

• Delgado V, Ajmone Marsan N, de Waha S, Bonaros N, Brida M, Burri H, Caselli S, Doenst T, Ederhy S, Erba PA, Foldager D, Fosbol EL, Kovac J, Mestres CA, Miller OI, Miro JM, Pazdernik M, Pizzi MN, Quintana E, Rasmussen TB, Ristic AD, Rodes-Cabau J, Sionis A, Zuhlke LJ, Borger MA; ESC Scientific Document Group. 2023 ESC Guidelines for the management of endocarditis. Eur Heart J. 2023 Oct 14;44(39):3948-4042. doi: 10.1093/eurheartj/ehad193. No abstract available.

  PMID: 37622656 BACKGROUND

• Milman A, Wieder-Finesod A, Zahavi G, Meitus A, Kariv S, Shafir Y, Beinart R, Rahav G, Nof E. Complicated Pocket Infection in Patients Undergoing Lead Extraction: Characteristics and Outcomes. J Clin Med. 2023 Jun 29;12(13):4397. doi: 10.3390/jcm12134397.

  PMID: 37445433 BACKGROUND

• Kusumoto FM, Schoenfeld MH, Wilkoff BL, Berul CI, Birgersdotter-Green UM, Carrillo R, Cha YM, Clancy J, Deharo JC, Ellenbogen KA, Exner D, Hussein AA, Kennergren C, Krahn A, Lee R, Love CJ, Madden RA, Mazzetti HA, Moore JC, Parsonnet J, Patton KK, Rozner MA, Selzman KA, Shoda M, Srivathsan K, Strathmore NF, Swerdlow CD, Tompkins C, Wazni O. 2017 HRS expert consensus statement on cardiovascular implantable electronic device lead management and extraction. Heart Rhythm. 2017 Dec;14(12):e503-e551. doi: 10.1016/j.hrthm.2017.09.001. Epub 2017 Sep 15. No abstract available.

  PMID: 28919379 BACKGROUND

• Blomstrom-Lundqvist C, Traykov V, Erba PA, Burri H, Nielsen JC, Bongiorni MG, Poole J, Boriani G, Costa R, Deharo JC, Epstein LM, Saghy L, Snygg-Martin U, Starck C, Tascini C, Strathmore N; ESC Scientific Document Group. European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Europace. 2020 Apr 1;22(4):515-549. doi: 10.1093/europace/euz246.

  PMID: 31702000 BACKGROUND

• Polewczyk A, Jachec W, Polewczyk M, Nowosielecka D, Brzozowski W, Kutarski A. Outcomes in patients with definite and possible infective endocarditis related to a cardiac implantable electronic device. Pol Arch Intern Med. 2024 Aug 8;134(7-8):16775. doi: 10.20452/pamw.16775. Epub 2024 Jun 17.

  PMID: 38895973 BACKGROUND

• Bongiorni MG, Kennergren C, Butter C, Deharo JC, Kutarski A, Rinaldi CA, Romano SL, Maggioni AP, Andarala M, Auricchio A, Kuck KH, Blomstrom-Lundqvist C; ELECTRa Investigators. The European Lead Extraction ConTRolled (ELECTRa) study: a European Heart Rhythm Association (EHRA) Registry of Transvenous Lead Extraction Outcomes. Eur Heart J. 2017 Oct 21;38(40):2995-3005. doi: 10.1093/eurheartj/ehx080.

  PMID: 28369414 BACKGROUND

• Chmielarczyk A, Pomorska-Wesolowska M, Romaniszyn D, Wojkowska-Mach J. Healthcare-Associated Laboratory-Confirmed Bloodstream Infections-Species Diversity and Resistance Mechanisms, a Four-Year Retrospective Laboratory-Based Study in the South of Poland. Int J Environ Res Public Health. 2021 Mar 9;18(5):2785. doi: 10.3390/ijerph18052785.

  PMID: 33803428 BACKGROUND

• Joshi S, Shallal A, Zervos M. Vancomycin-Resistant Enterococci: Epidemiology, Infection Prevention, and Control. Infect Dis Clin North Am. 2021 Dec;35(4):953-968. doi: 10.1016/j.idc.2021.07.002.

  PMID: 34752227 BACKGROUND

• Cerini P, Meduri FR, Tomassetti F, Polidori I, Brugneti M, Nicolai E, Bernardini S, Pieri M, Broccolo F. Trends in Antibiotic Resistance of Nosocomial and Community-Acquired Infections in Italy. Antibiotics (Basel). 2023 Mar 24;12(4):651. doi: 10.3390/antibiotics12040651.

  PMID: 37107013 BACKGROUND

Related Links

• Lekooporność Streptococcus pneumoniae: częstość występowania, mechanizmy, znaczenie kliniczne. Aktualności Narodowego Programu Ochrony Antybiotyków 2019; 2: 1-9.
• Food and Drug Administration Orbactiv
• European Medicines Agency Orbactiv.

MeSH Terms

Conditions

Endocarditis; Gram-Positive Bacterial Infections; Cross Infection

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Beata Sarecka-Hujar, Professor

  Department of Basic Biomedical Science, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Poland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danuta Loboda, MD, PhD

CONTACT

(+48) 32 359-89-90; dloboda@sum.edu.pl

Beata Sarecka-Hujar, Professor

CONTACT

bsarecka-hujar@sum.edu.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The study will be blinded only at the randomization stage. A different time model for antibiotic dosing does not allow for blinding of the Care Provider and allows the Participant to easily identify the type of antibiotic administered based on the information obtained in the consent form for the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized 1:1 to the intervention and control groups. Experimental group: Oritavancin dosage in superficial ABSSSI or PI: Single dose of 1,200 mg (3 vials) administered as a 3-hour intravenous infusion. Oritavancin dosage in LRIE: First dose of 1,200 mg (3 vials) administered as a 3-hour intravenous infusion, subsequent doses of 800 mg (2 vials) administered as a 2-3 hour intravenous infusion at 7-day intervals, to achieve the required duration of drug therapy of 2-6 weeks (counted from the day of transvenous lead extraction). Control group: Vancomycin dosage: Repeated doses of 15-20 mg/kg body weight every 8-12 hours administered as an hourly intravenous infusion for 7-10 days in ABSSSI, for 10-14 days in PI, and for 2-6 weeks in LRIE.

Study Record Dates

• First Submitted: May 12, 2025
• First Posted: June 10, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: A link to the IPD data that underlie results in a publication will be available immediately after the manuscript is accepted and published.
• Access Criteria: The raw IPD data and supporting Information will be openly available in the Polish Platform of Medical Research (https://ppm.edu.pl/search/researchdata?ps=20\&t=simple\&showRel=false\&lang=pl\&qp=\&cid=1577414) under the CC BY license.

Locations

PL (1)