Antibiotics Continuous Infusion at Home (TAID)
Primary Purpose
Severe Bacterial Infections
Status
Not yet recruiting
Phase
Phase 1
Locations
Italy
Study Type
Interventional
Intervention
Cefepime
Piperacillin/tazobactam
Meropenem
Vancomycin
Sponsored by
About this trial
This is an interventional treatment trial for Severe Bacterial Infections
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- ASST Santi Paolo Carlo - San Carlo Borromeo Hospital - SSd Onco-Hematology
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Arm A - Cefepime
Arm B - Piperacillin/tazobactam
Arm C - Meropenem
Arm D - Vancomycin
Arm Description
Continuous infusion of Cefepime at home.
Continuous infusion of Piperacillin/tazobactam at home.
Continuous infusion of meropenem at home.
Continuous infusion of vancomycin at home.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Effectiveness of antibiotic treatment
The effectiveness of antibiotic treatment in continuous infusion at home will be compared with the effectiveness of antibiotic standard treatment in terms of the number of patients that have to start a new antibiotic line therapy.
Number of new hospitalizations days for the same problem in the month following the start of home continuous infusion therapy.
The number of new hospitalizations days for the same problem in the month following the start of continuous infusion antibiotic therapy at home will be compared with the number of new hospitalizations for the same problem with antibiotic standard treatment.
Ongoing adverse events of home continuos infusion therapy.
The number of adverse events of each grade will be quantified.
Adverse events related to the presence of a venous access
The number of adverse events related to the presence of a venous access will be quantified.
Full Information
NCT ID
NCT04816968
First Posted
March 22, 2021
Last Updated
March 24, 2021
Sponsor
Ospedale San Carlo Borromeo
Collaborators
Associazione Oncologica Milanese AmoLaVita ONLUS
1. Study Identification
Unique Protocol Identification Number
NCT04816968
Brief Title
Antibiotics Continuous Infusion at Home
Acronym
TAID
Official Title
TAID Study - A Prospective Interventional Trial on Antibiotics Continuous Infusion at Home
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2021 (Anticipated)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ospedale San Carlo Borromeo
Collaborators
Associazione Oncologica Milanese AmoLaVita ONLUS
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
Detailed Description
STATISTICAL ANALYSIS: This is an interventional monocentric study. The primary endpoint of the study is a reduction in hospitalization days. The study population is divided into 4 treatment arms: assuming that the average length of hospitalization for the standard treatment of a severe infection, for each of the types of antibiotic studied, is 14 days, with the treatment envisaged by the study it is assumed to reduce this duration,for all 4 treatment arms, to a number equal to or less than 12 days. With these premises, applying the One sample t-test design method, assuming α = 0.05 and β = 0.1, the number of patients expected is 9 for each treatment arm. Considering a 30% dropout, the total population to be enrolled for each type of antibiotic is 12 patients. In total, the study will enroll 48 patients. The study provides for an observation period of 30 days from enrollment. During this period, efficacy, safety and pharmacokinetic data will be collected for each treatment arm.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Bacterial Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm A - Cefepime
Arm Type
Experimental
Arm Description
Continuous infusion of Cefepime at home.
Arm Title
Arm B - Piperacillin/tazobactam
Arm Type
Experimental
Arm Description
Continuous infusion of Piperacillin/tazobactam at home.
Arm Title
Arm C - Meropenem
Arm Type
Experimental
Arm Description
Continuous infusion of meropenem at home.
Arm Title
Arm D - Vancomycin
Arm Type
Experimental
Arm Description
Continuous infusion of vancomycin at home.
Intervention Type
Drug
Intervention Name(s)
Cefepime
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Piperacillin/tazobactam
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Meropenem
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Vancomycin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of hospitalization days for the treatment of severe bacterial infections
Description
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.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Effectiveness of antibiotic treatment
Description
The effectiveness of antibiotic treatment in continuous infusion at home will be compared with the effectiveness of antibiotic standard treatment in terms of the number of patients that have to start a new antibiotic line therapy.
Time Frame
30 days from the enrollment
Title
Number of new hospitalizations days for the same problem in the month following the start of home continuous infusion therapy.
Description
The number of new hospitalizations days for the same problem in the month following the start of continuous infusion antibiotic therapy at home will be compared with the number of new hospitalizations for the same problem with antibiotic standard treatment.
Time Frame
30 days from the enrollment
Title
Ongoing adverse events of home continuos infusion therapy.
Description
The number of adverse events of each grade will be quantified.
Time Frame
30 days from the enrollment
Title
Adverse events related to the presence of a venous access
Description
The number of adverse events related to the presence of a venous access will be quantified.
Time Frame
30 days from the enrollment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vittorio Montefusco, MD
Phone
+39 02 4022 2104
Email
vittorio.montefusco@asst-santipaolocarlo.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vittorio Motefusco, MD
Organizational Affiliation
Ospedale San Carlo Borromeo
Official's Role
Principal Investigator
Facility Information:
Facility Name
ASST Santi Paolo Carlo - San Carlo Borromeo Hospital - SSd Onco-Hematology
City
Milan
ZIP/Postal Code
20153
Country
Italy
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vittorio Montefusco, MD
First Name & Middle Initial & Last Name & Degree
Vittorio Montefusco, MD
First Name & Middle Initial & Last Name & Degree
Teresa Bini, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
23074314
Citation
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Results Reference
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PubMed Identifier
11939682
Citation
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.
Results Reference
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PubMed Identifier
16940077
Citation
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Results Reference
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PubMed Identifier
17205441
Citation
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.
Results Reference
background
PubMed Identifier
29982449
Citation
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.
Results Reference
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Citation
Care of the elderly patient. J. Hosp. Med 2006;1;60-61
Results Reference
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PubMed Identifier
21545741
Citation
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.
Results Reference
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PubMed Identifier
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Citation
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.
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PubMed Identifier
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Citation
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.
Results Reference
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Antibiotics Continuous Infusion at Home
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