Antibiotics Continuous Infusion at Home

NCT04816968 | Unknown Phase 1

• 1 other identifier: TAID Study
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

BACKGROUND: The spread of multidrug-resistant bacteria represents a well-known problem, which must be face up by optimizing antibiotic therapy both in terms of choosing the most appropriate drug and of an adequate treatment duration. The method of administration is also a critical element. There are data relating to the maximization of the efficacy of Carbapenems and Piperacillin/Tazobactam by continuous infusion, able to constantly maintain adequate drug concentrations. Several studies, conducted comparing a standard administration of Carbapenem or Piperacillin/Tazobactam to an extended administration or continuous perfusion to evaluate safety and efficacy in terms of mortality reduction, have been documented. The achievement of optimal serum concentrations during continuous infusion has been documented both for Carbapenems and Piperacillin/Tazobactam, and for other types of antibiotics such as Cefepime and Vancomycin. The duration of antibiotic treatment is a critical factor for the prevention of relapses as well as the onset of resistance. The recommended duration of antibiotic treatment varies according to the site of infection and the type of pathogen and is generally between 7 and 14 days, however, in particular cases it is possible that the administration of antibiotics must be longer than one month. In general, the length of hospitalization is associated with a greater likelihood of complications for patients, with a substantial increase in the risk of developing multiple types of complications, such nosocomial infections, bed rest, bedsores, falls, malnutrition and disorientation. It should also be noted that prolonged hospitalization leads to a substantial increase in care costs. The advantage in terms of greater therapeutic success linked to the continuous infusion of some types of antibiotics has been used for the development of home infusion protocols for antibiotic therapy. There are numerous studies that show the feasibility and effectiveness of home infusion antibiotic therapy using elastomeric devices, documenting its substantial equivalence with respect to hospital treatment. The antibiotics for which there is evidence of feasibility are various, including Cefepime, Vancomycin and Piperacillin/Tazobactam. STUDY DESIGN: The study is aimed to patients with severe bacterial infections who have started an antibiotic treatment and are benefiting from such therapy. The purpose of the study is to move the continuation of antibiotic therapy to the home setting once its efficacy and tolerability during hospitalization have been documented, in order to allow the patient a potentially eradicating treatment, of adequate duration without the need of hospitalization. Patients are enrolled when the efficacy and tolerability of the ongoing antibiotic treatment based on Cefepime, Meropenem, Piperacillin/Tazobactam or Vancomycin has been documented. The protocol requires that the patient go to the hospital every morning to replace the elastomer and to carry out a medical examination. Blood chemistry tests, which include at least blood counts, electrolytes, renal function, liver function and inflammation indices are scheduled to be performed at least once a week. Exams can also be done more frequently based on clinical needs. Antibiotic therapy should be carried out until the infection is cured, as per current clinical practice. For the purposes of the study, the patient remains under observation for 30 days after enrollment. Blood samples for the assessment of antibiotic concentrations will be performed in correspondence with the blood chemistry tests performed routinely for patient assessment. In any case, for each patient, a sample is taken for the dosage of the antibiotic used, which will be a single sample in the event of a continuous infusion, or a downstream sample (within one hour of the new antibiotic administration) and peak (30 minutes after the end of the infusion). The pharmacokinetic sampling relating to the outpatient phase will be carried out on the third or fourth day of continuous infusion therapy at the time of the elastomer change.

Conditions

Severe Bacterial Infections

Outcome Measures

Primary Outcomes (1)

• Number of hospitalization days for the treatment of severe bacterial infections

  The number of hospitalization days for the treatment of severe bacterial infections with continuous infusion antibiotics at home will be compared with the number of hospitalization days for standard antibiotics therapies for severe bacterial infections.

  14 days

Secondary Outcomes (4)

• Effectiveness of antibiotic treatment

  30 days from the enrollment

• Number of new hospitalizations days for the same problem in the month following the start of home continuous infusion therapy.

  30 days from the enrollment

• Ongoing adverse events of home continuos infusion therapy.

  30 days from the enrollment

• Adverse events related to the presence of a venous access

  30 days from the enrollment

Study Arms (4)

Arm A - Cefepime

EXPERIMENTAL

Continuous infusion of Cefepime at home.

Drug: Cefepime

Arm B - Piperacillin/tazobactam

EXPERIMENTAL

Continuous infusion of Piperacillin/tazobactam at home.

Drug: Piperacillin/tazobactam

Arm C - Meropenem

EXPERIMENTAL

Continuous infusion of meropenem at home.

Drug: Meropenem

Arm D - Vancomycin

EXPERIMENTAL

Continuous infusion of vancomycin at home.

Drug: Vancomycin

Interventions

Cefepime DRUG

Cefepime from 3 to 6 gr, based on patient's clinical status, reduced dose based on organ function and physician discretion, in 100cc saline solution in elastomer, perfused in 24 hours.

Arm A - Cefepime

Piperacillin/tazobactam DRUG

Piperacillin/Tazobactam 18 gr, based on patient's clinical status, reduced dose based on organ function and physician discretion, in 100cc saline solution in elastomer, perfused in 24 hours.

Arm B - Piperacillin/tazobactam

Meropenem DRUG

Meropenem 3 gr, based on patient's clinical status, reduced dose based on organ function and physician discretion, in 100cc saline solution in elastomer, perfused in 24 hours.

Arm C - Meropenem

Vancomycin DRUG

Vancomycin 30 mg/kg, based on patient's clinical status, reduced dose based on organ function and physician discretion, in 100cc saline solution in elastomer, perfused in 24 hours.

Arm D - Vancomycin

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 to 90 years.
• Ability to understand and sign informed consent.
• Treatment infection responsive to Cefepime, Meropenem or Piperacillin / Tazobactam, Vancomycin.
• Absence of allergies to Cefepime, Meropenem or Piperacillin / Tazobactam, Vancomycin.
• Evidence of clinical response to treatment with Cefepime, Meropenem or Piperacillin / Tazobactam, Vancomycin and at least 3 days of apyrexia with current infusion antibiotic therapy.
• Good tolerance to ongoing antibiotic treatment with Cefepime, Meropenem or Piperacillin / Tazobactam, Vancomycin.

You may not qualify if:

• Inability for any reason (e.g. absence of caregiver) to manage the elastomeric pump and access the hospital on a daily basis.
• Lack of adequate venous access.
• Inability to hydrate themselves properly orally.
• Infection involving the central nervous system.
• Creatinine\> 2 mg / dL.
• Neutrophil granulocytes ≤ 1000 / µL.
• Platelets ≤ 20000 / µL.
• "aspartate amino transferase" and "alanine amino transferase" \> 100 U / L.
• Bilirubin\> 3 mg / dL.
• Presence of any comorbidities that, in the opinion of the physician, could compromise the safe execution of antibiotic home continuous infusion.

Sponsors & Collaborators

• Ospedale San Carlo Borromeo: lead
• Associazione Oncologica Milanese AmoLaVita ONLUS: collaborator

Study Sites (1)

ASST Santi Paolo Carlo - San Carlo Borromeo Hospital - SSd Onco-Hematology

Milan, 20153, Italy

Location

Related Publications (9)

• Falagas ME, Tansarli GS, Ikawa K, Vardakas KZ. Clinical outcomes with extended or continuous versus short-term intravenous infusion of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis. Clin Infect Dis. 2013 Jan;56(2):272-82. doi: 10.1093/cid/cis857. Epub 2012 Oct 16.

  PMID: 23074314 BACKGROUND

• Grant EM, Kuti JL, Nicolau DP, Nightingale C, Quintiliani R. Clinical efficacy and pharmacoeconomics of a continuous-infusion piperacillin-tazobactam program in a large community teaching hospital. Pharmacotherapy. 2002 Apr;22(4):471-83. doi: 10.1592/phco.22.7.471.33665.

  PMID: 11939682 BACKGROUND

• Lau WK, Mercer D, Itani KM, Nicolau DP, Kuti JL, Mansfield D, Dana A. Randomized, open-label, comparative study of piperacillin-tazobactam administered by continuous infusion versus intermittent infusion for treatment of hospitalized patients with complicated intra-abdominal infection. Antimicrob Agents Chemother. 2006 Nov;50(11):3556-61. doi: 10.1128/AAC.00329-06. Epub 2006 Aug 28.

  PMID: 16940077 BACKGROUND

• Lodise TP Jr, Lomaestro B, Drusano GL. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin Infect Dis. 2007 Feb 1;44(3):357-63. doi: 10.1086/510590. Epub 2007 Jan 2.

  PMID: 17205441 BACKGROUND

• Voumard R, Gardiol C, Andre P, Arensdorff L, Cochet C, Boillat-Blanco N, Decosterd L, Buclin T, de Valliere S. Efficacy and safety of continuous infusions with elastomeric pumps for outpatient parenteral antimicrobial therapy (OPAT): an observational study. J Antimicrob Chemother. 2018 Sep 1;73(9):2540-2545. doi: 10.1093/jac/dky224.

  PMID: 29982449 BACKGROUND

• Care of the elderly patient. J. Hosp. Med 2006;1;60-61

  BACKGROUND

• Lagoe RJ, Johnson PE, Murphy MP. Inpatient hospital complications and lengths of stay: a short report. BMC Res Notes. 2011 May 5;4:135. doi: 10.1186/1756-0500-4-135.

  PMID: 21545741 BACKGROUND

• Hoogervorst-Schilp J, Langelaan M, Spreeuwenberg P, de Bruijne MC, Wagner C. Excess length of stay and economic consequences of adverse events in Dutch hospital patients. BMC Health Serv Res. 2015 Dec 1;15:531. doi: 10.1186/s12913-015-1205-5.

  PMID: 26626729 BACKGROUND

• Manning L, Wright C, Ingram PR, Whitmore TJ, Heath CH, Manson I, Page-Sharp M, Salman S, Dyer J, Davis TM. Continuous infusions of meropenem in ambulatory care: clinical efficacy, safety and stability. PLoS One. 2014 Jul 14;9(7):e102023. doi: 10.1371/journal.pone.0102023. eCollection 2014.

  PMID: 25019523 BACKGROUND

MeSH Terms

Conditions

Bacterial Infections

Interventions

Cefepime; Piperacillin, Tazobactam Drug Combination; Meropenem; Vancomycin

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tazobactam; Penicillanic Acid; Penicillins; Piperacillin; Ampicillin; Penicillin G; Sulfones; Drug Combinations; Pharmaceutical Preparations; Thienamycins; Carbapenems; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Vittorio Motefusco, MD

  Ospedale San Carlo Borromeo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vittorio Montefusco, MD

CONTACT

+39 02 4022 2104; vittorio.montefusco@asst-santipaolocarlo.it

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director Ssd of Oncohematology

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: March 25, 2021
• Study Start: September 1, 2021
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2023
• Last Updated: March 25, 2021

Record last verified: 2021-03

Locations

IT (1)