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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03941951
Other study ID # FIS-TED-2019-01
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date July 9, 2019
Est. completion date December 31, 2022

Study information

Verified date May 2020
Source Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Contact Zaira Palacios Baena
Phone 34 653276353
Email zaira.palacios.baena@hotmail.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Quasi-experimental intervention multicenter trial of patients treated with new antibiotics (before-after study).

The study will be carried out in 14 hospitals of the Andalusian Public Health System with representation from all the provinces and has been designed in two phases:

1. A first phase in which an observational study of historical preintervention cohorts of patients who have received either empirical or targeted treatment with ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam, ceftolozane-tazobactam and isavuconazole from January 2016 to December 2019 will be developed. Case detection will be carried out by locating the antimicrobial prescriptions in the electronic prescribing systems and / or pharmaceutical management systems of each hospital. A set of epidemiological, clinical, microbiological and prognostic variables will be completed in each case.

2. A second phase or intervention period that will be applied to the cohort of patients treated with new antibiotics (intervention cohort) from January 2020 to June 2021. A quasi-experimental intervention study will be carried out through the development of a Program for Optimizing the use of Antibiotics (PROA) in Spanish, Antimicrobial Stewardship Program (ASP) in English, in the participating hospitals. It will consist in the development of a consensus document on the use of new antibiotics following a Delphi methodology, dissemination of the consensus document / guide among the participating hospitals and audit on the prescription of new antimicrobials after the implementation of the guide based on providing non-imposition advice and positive reinforcement to the prescriber. The recommendations will be consigned in a structured form, which will allow to evaluate the degree of follow-up of the recommendations. The audit will be performed on day 0-1 of the prescription.

3. Cohort of bacteremia due to multiresistant microorganisms ("safety" cohort): In order to evaluate the safety of the use of new antimicrobials against therapeutic alternatives in syndromes where they are potentially a preferred option and parallel to the two phases, episodes for bacteremia by carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, carbapenem-resistant enterobacteria, vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus occurred in participating hospitals from 2017 to 2021 will be collected.


Recruitment information / eligibility

Status Recruiting
Enrollment 900
Est. completion date December 31, 2022
Est. primary completion date December 31, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Pre-intervention cohort (historical):

Inclusion criteria:

- All patients treated with ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam, ceftolozane-tazobactam or isavuconazole.

- In a hospital or ambulatory regime.

- That they have received at least 1 dose of treatment of any of the antimicrobials mentioned, either as empirical or directed treatment.

- Adults (18 years).

- Between January 1, 2016 and December 31, 2019.

Exclusion criteria:

• There are no exclusion criteria except for age.

Intervention cohort:

Inclusion criteria:

- All patients treated with ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam, ceftolozane-tazobactam or isavuconazole.

- In a hospital or ambulatory regime.

- That they have received at least 1 dose of treatment of any of the antimicrobials mentioned, either as empirical or directed treatment.

- Adults (18 years).

- From January 1, 2020 to December 31, 2021.

- Since the publication and diffusion of the recommendation guide.

Exclusion criteria:

• There are no exclusion criteria except for age.

Safety cohort:

Inclusion criteria:

- All episodes of clinically significant bacteremia (that have received any treatment) produced by:

- Acinetobacter baumannii resistant or with intermediate susceptibility to any carbapenem.

- Pseudomonas aeruginosa resistant or with intermediate susceptibility to any carbapenem.

- Enterobacteria resistant or with intermediate susceptibility to any carbapenem.

- Vancomycin-resistant Enterococcus faecium.

- Methicillin-resistant Staphylococcus aureus.

- From January 1, 2017 to December 31, 2021.

- Adult patients (18 years old).

Exclusion criteria:

• There are no exclusion criteria except for age.

Study Design


Intervention

Behavioral:
Non-impositive Program for Optimizing the Use of Antimicrobials
Quasi-experimental intervention through the development of a Program for Optimizing the Use of Antimicrobials in the participating hospitals. The intervention will consist of the development of a consensus guide on the use of new antibiotics, its dissemination in Andalusian hospitals and an audit on the prescription of new antibiotics.

Locations

Country Name City State
Spain Hospital de Poniente-El Ejido Almería
Spain University Hospital Puerta del Mar Cadiz
Spain University Hospital Reina Sofía Córdoba
Spain Hospital Clínico Universitario San Cecilio Granada
Spain University Hospital Virgen de las Nieves Granada
Spain Área Hospitalaria Juan Ramón Jiménez Huelva
Spain Complejo Hospitalario de Jaén Jaén
Spain University Hospital de Jerez de la Frontera Jerez De La Frontera
Spain Hospital Regional Universitario de Málaga Málaga
Spain University Hospital Virgen de la Victoria Málaga
Spain Hospital de Puerto Real Puerto Real
Spain University Hospital Virgen de Valme Sevilla
Spain University Hospital Virgen del Rocío Sevilla
Spain University Hospital Virgen Macarena (Sevilla). Sevilla

Sponsors (1)

Lead Sponsor Collaborator
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Country where clinical trial is conducted

Spain, 

References & Publications (34)

Bouza E, Valerio M, Soriano A, Morata L, Carus EG, Rodríguez-González C, Hidalgo-Tenorio MC, Plata A, Muñoz P, Vena A; DALBUSE Study Group (Dalbavancina: Estudio de su uso clinico en España). Dalbavancin in the treatment of different gram-positive infections: a real-life experience. Int J Antimicrob Agents. 2018 Apr;51(4):571-577. doi: 10.1016/j.ijantimicag.2017.11.008. Epub 2017 Nov 24. — View Citation

Cosimi RA, Beik N, Kubiak DW, Johnson JA. Ceftaroline for Severe Methicillin-Resistant Staphylococcus aureus Infections: A Systematic Review. Open Forum Infect Dis. 2017 May 2;4(2):ofx084. doi: 10.1093/ofid/ofx084. eCollection 2017 Spring. Review. — View Citation

Davey P, Marwick CA, Scott CL, Charani E, McNeil K, Brown E, Gould IM, Ramsay CR, Michie S. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev. 2017 Feb 9;2:CD003543. doi: 10.1002/14651858.CD003543.pub4. Review. — View Citation

De León-Borrás R, Álvarez-Cardona J, Vidal JA, Guiot HM. Ceftazidime/Avibactam for Refractory Bacteremia, Vertebral Diskitis/Osteomyelitis with Pre-Vertebral Abscess and Bilateral Psoas Pyomyositis Secondary to Klebsiella Pneumoniae Carbapenemase-Producing Bacteria (KPC). P R Health Sci J. 2018 Jun;37(2):128-131. — View Citation

Diamond IR, Grant RC, Feldman BM, Pencharz PB, Ling SC, Moore AM, Wales PW. Defining consensus: a systematic review recommends methodologic criteria for reporting of Delphi studies. J Clin Epidemiol. 2014 Apr;67(4):401-9. doi: 10.1016/j.jclinepi.2013.12.002. Review. — View Citation

Dietl B, Sánchez I, Arcenillas P, Cuchi E, Gómez L, González de Molina FJ, Boix-Palop L, Nicolás J, Calbo E. Ceftolozane/tazobactam in the treatment of osteomyelitis and skin and soft-tissue infections due to extensively drug-resistant Pseudomonas aeruginosa: clinical and microbiological outcomes. Int J Antimicrob Agents. 2018 Mar;51(3):498-502. doi: 10.1016/j.ijantimicag.2017.11.003. Epub 2017 Nov 20. — View Citation

European Centre for Disease Prevention and Control. Rapid risk assessment: Carbapenem-resistant Enterobacteriaceae - first update 4 June 2018. Stockholm: ECDC; 2018. https://ecdc.europa.eu/sites/portal/files/documents/RRA-Enterobacteriaceae-Carbapenems-European-Union-countries.pdf

Ficha técnica de ceftarolina. https://ec.europa.eu/health/documents/communityregister/2012/20120823123835/anx_123835_es.pdf

Ficha técnica de ceftazidima-avibactam. http://www.ema.europa.eu/docs/es_ES /document_library /EPAR_-_Product_Information/human/004027/WC500210234.pdf

Ficha técnica de ceftolozano-tazobactam. https://ec.europa.eu/health/documents /communityregister/2015/20150918132786/anx_132786_es.pdf

Ficha técnica de isavuconazol. https://ec.europa.eu/health/documents/community-register/2015/20151015132781/anx_132781_es.pdf.

Ficha técnica de tedizolid. http://www.ema.europa.eu/docs/es_ES/document_library /EPAR_-_Product_Information/human/002846/WC500184802.pdf

Gaibani P, Campoli C, Lewis RE, Volpe SL, Scaltriti E, Giannella M, Pongolini S, Berlingeri A, Cristini F, Bartoletti M, Tedeschi S, Ambretti S. In vivo evolution of resistant subpopulations of KPC-producing Klebsiella pneumoniae during ceftazidime/avibactam treatment. J Antimicrob Chemother. 2018 Jun 1;73(6):1525-1529. doi: 10.1093/jac/dky082. — View Citation

Gofman N, To K, Whitman M, Garcia-Morales E. Successful treatment of ventriculitis caused by Pseudomonas aeruginosa and carbapenem-resistant Klebsiella pneumoniae with i.v. ceftazidime-avibactam and intrathecal amikacin. Am J Health Syst Pharm. 2018 Jul 1;75(13):953-957. doi: 10.2146/ajhp170632. — View Citation

Hernández-García I, Sáenz-González MC, Meléndez D. [Assessment of an educational program for the prevention of healthcare-associated infections]. Rev Calid Asist. 2013 Mar-Apr;28(2):96-108. doi: 10.1016/j.cali.2012.09.001. Epub 2012 Nov 2. Spanish. — View Citation

Iacovelli A, Spaziante M, Al Moghazi S, Giordano A, Ceccarelli G, Venditti M. A challenging case of carbapenemase-producing Klebsiella pneumoniae septic thrombophlebitis and right mural endocarditis successfully treated with ceftazidime/avibactam. Infection. 2018 Oct;46(5):721-724. doi: 10.1007/s15010-018-1166-9. Epub 2018 Jun 20. Erratum in: Infection. 2018 Jul 10;:. — View Citation

Informa de posicionamiento terapéutico de dalbavancina. https://www.aemps.gob.es/medicamentosUsoHumano/informesPublicos/docs/IPTdalbavancina-Xydalba.pdf

López Cortés LE, Mujal Martínez A, Fernández Martínez de Mandojana M, Martín N, Gil Bermejo M, Solà Aznar J, Villegas Bruguera E, Peláez Cantero MJ, Retamar Gentil P, Delgado Vicente M, González-Ramallo VJ, Ponce González MÁ, Mirón Rubio M, Gómez Rodríguez de Mendarozqueta MM, Goenaga Sánchez MÁ, Sanroma Mendizábal P, Delgado Mejía E, Pajarón Guerrero M; Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), the Sociedad Española de Hospitalización a Domicilio (SEHAD) Group. Executive summary of outpatient parenteral antimicrobial therapy: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases and the Spanish Domiciliary Hospitalisation Society. Enferm Infecc Microbiol Clin. 2019 Jun - Jul;37(6):405-409. doi: 10.1016/j.eimc.2018.03.012. Epub 2018 May 18. English, Spanish. — View Citation

López-Cerero L, Egea P, Gracia-Ahufinger I, González-Padilla M, Rodríguez-López F, Rodríguez-Baño J, Pascual A. Characterisation of the first ongoing outbreak due to KPC-3-producing Klebsiella pneumoniae (ST512) in Spain. Int J Antimicrob Agents. 2014 Dec;44(6):538-40. doi: 10.1016/j.ijantimicag.2014.08.006. Epub 2014 Sep 26. — View Citation

Mensa J, Soriano A, Llinares P, Barberán J, Montejo M, Salavert M, Alvarez-Rocha L, Maseda E, Moreno A, Pasquau J, Gómez J, Parra J, Candel J, Azanza JR, García JE, Marco F, Soy D, Grau S, Arias J, Fortún J, de Alarcón CA, Picazo J; Sociedad Española de Quimioterapia (SEQ); Sociedad Española de Medicina Interna (SEMI); GTIPO-Sociedad Española de Anestesiología y Reanimación. [Guidelines for antimicrobial treatment of the infection by Staphylococcus aureus]. Rev Esp Quimioter. 2013 Jan;26 Suppl 1:1-84. Review. Spanish. — View Citation

Nigo M, Luce AM, Arias CA. Long-term Use of Tedizolid as Suppressive Therapy for Recurrent Methicillin-Resistant Staphylococcus aureus Graft Infection. Clin Infect Dis. 2018 Jun 1;66(12):1975-1976. doi: 10.1093/cid/ciy041. — View Citation

PIRASOA: actividad laboratorio de referencia. Accesible en: pirasoa.iavante.es/mod/resource/view.php?id=797

Plan estratégico y de acción para reducir el riesgo de selección y diseminación de la resistencia a los antibióticos http://www.resistenciaantibioticos.es/es/system/files/ content_images/plan_nacional_resistencia_antibioticos.pdf

Plant AJ, Dunn A, Porter RJ. Ceftolozane-tazobactam resistance induced in vivo during the treatment of MDR Pseudomonas aeruginosa pneumonia. Expert Rev Anti Infect Ther. 2018 May;16(5):367-368. doi: 10.1080/14787210.2018.1473079. — View Citation

Rodríguez-Baño J, Cisneros JM, Cobos-Trigueros N, Fresco G, Navarro-San Francisco C, Gudiol C, Horcajada JP, López-Cerero L, Martínez JA, Molina J, Montero M, Paño-Pardo JR, Pascual A, Peña C, Pintado V, Retamar P, Tomás M, Borges-Sa M, Garnacho-Montero J, Bou G; Study Group of Nosocomial Infections (GEIH) of the Spanish Society of Infectious Diseases, Infectious Diseases (SEIMC). Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology. Enferm Infecc Microbiol Clin. 2015 May;33(5):337.e1-337.e21. doi: 10.1016/j.eimc.2014.11.009. Epub 2015 Jan 15. — View Citation

Rodríguez-Baño J, Gutiérrez-Gutiérrez B, Machuca I, Pascual A. Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae. Clin Microbiol Rev. 2018 Feb 14;31(2). pii: e00079-17. doi: 10.1128/CMR.00079-17. Print 2018 Apr. Review. — View Citation

Rodríguez-Baño J, Paño-Pardo JR, Alvarez-Rocha L, Asensio Á, Calbo E, Cercenado E, Cisneros JM, Cobo J, Delgado O, Garnacho-Montero J, Grau S, Horcajada JP, Hornero A, Murillas-Angoiti J, Oliver A, Padilla B, Pasquau J, Pujol M, Ruiz-Garbajosa P, San Juan R, Sierra R; GEIH-SEIMC; SEFH; SEMPSPH. [Programs for optimizing the use of antibiotics (PROA) in Spanish hospitals: GEIH-SEIMC, SEFH and SEMPSPH consensus document]. Farm Hosp. 2012 Jan-Feb;36(1):33.e1-30. doi: 10.1016/j.farma.2011.10.001. Epub 2011 Dec 1. Spanish. — View Citation

Si S, Durkin MJ, Mercier MM, Yarbrough ML, Liang SY. Successful Treatment of Prosthetic Joint Infection due to Vancomycin-resistant Enterococci with Tedizolid. Infect Dis Clin Pract (Baltim Md). 2017 Mar;25(2):105-107. doi: 10.1097/IPC.0000000000000469. — View Citation

Spellberg B, Bonomo RA. Editorial Commentary: Ceftazidime-Avibactam and Carbapenem-Resistant Enterobacteriaceae: "We're Gonna Need a Bigger Boat". Clin Infect Dis. 2016 Dec 15;63(12):1619-1621. Epub 2016 Sep 13. — View Citation

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. — View Citation

Tobudic S, Forstner C, Burgmann H, Lagler H, Ramharter M, Steininger C, Vossen MG, Winkler S, Thalhammer F. Dalbavancin as Primary and Sequential Treatment for Gram-Positive Infective Endocarditis: 2-Year Experience at the General Hospital of Vienna. Clin Infect Dis. 2018 Aug 16;67(5):795-798. doi: 10.1093/cid/ciy279. — View Citation

Versporten A, Zarb P, Caniaux I, Gros MF, Drapier N, Miller M, Jarlier V, Nathwani D, Goossens H; Global-PPS network. Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries: results of an internet-based global point prevalence survey. Lancet Glob Health. 2018 Jun;6(6):e619-e629. doi: 10.1016/S2214-109X(18)30186-4. Epub 2018 Apr 23. Erratum in: Lancet Glob Health. 2018 Sep;6(9):e968. — View Citation

Vickery SB, McClain D, Wargo KA. Successful Use of Ceftolozane-Tazobactam to Treat a Pulmonary Exacerbation of Cystic Fibrosis Caused by Multidrug-Resistant Pseudomonas aeruginosa. Pharmacotherapy. 2016 Oct;36(10):e154-e159. doi: 10.1002/phar.1825. Epub 2016 Sep 1. — View Citation

Zasowski EJ, Trinh TD, Claeys KC, Casapao AM, Sabagha N, Lagnf AM, Klinker KP, Davis SL, Rybak MJ. Multicenter Observational Study of Ceftaroline Fosamil for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections. Antimicrob Agents Chemother. 2017 Jan 24;61(2). pii: e02015-16. doi: 10.1128/AAC.02015-16. Print 2017 Feb. — View Citation

* Note: There are 34 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Total antibiotic consumption Defined daily doses (DDD) of each antibiotic per 1000 stays Yearly from date of intervention up to 24 months of follow-up
Secondary Total cost per antimicrobial Total expense in euros of each antimicrobial per 1000 stays Yearly from date of intervention up to 24 months of follow-up
Secondary Mortality rate Mortality from any cause at 7, 14 and 30 days after the start of the treatment. At 7, 14 and 30 days after the start of the treatment.
Secondary Total length of hospital stay Duration of a single episode of hospitalization defined as the time between hospital admission and discharge measured in days. During this episode the patient has to be prescribed with one of the antibiotics included in the study. Monthly from date of intervention up to 24 months of follow-up
Secondary Incidence of colitis due to Clostridium difficile. Clostridium difficile infection documented during treatment with any of the antibiotics described Monthly from date of intervention up to 24 months of follow-up
Secondary Percentage of patients with infections by multiresistant microorganisms. Colonization during treatment by resistant microorganisms Percentage of patients with infections by multiresistant microorganisms in each cohort. Monthly from date of intervention up to 24 months of follow-up
Secondary Percentage of patients colonized by multiresistant microorganisms Percentage of patients colonized by multiresistant microorganisms in each cohort after completion of treatment with antibiotic under study. Monthly from date of intervention up to 24 months of follow-up
Secondary Re-admission rate Re-admission of the patient in the hospital at 90 days after the start of the antibiotic treatment. 90 days after the start of the antibiotic treatment.
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