Clinical Trial Results:
A β-d-glucan guided antifungal stewardship strategy for the management of patients with severe abdominal sepsis. A monocentric interventional explorative study with a pharmacodynamic/pharmacokinetic substudy entitled:
“A Pilot Substudy of Liposomal Amphotericin B Pharmacodynamics in Patients with Abdominal Sepsis”
Summary
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EudraCT number |
2016-002335-14 |
Trial protocol |
IT |
Global end of trial date |
11 Sep 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Feb 2025
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First version publication date |
09 Feb 2025
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
LAMBDA
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
LAMBDA: LAMBDA | ||
Sponsors
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Sponsor organisation name |
IRCCS Azienda Ospedaliero-Universitaria di Bologna
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Sponsor organisation address |
Via Albertoni 15, Bologna, Italy, 40138
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Public contact |
Prof. Pierluigi Viale, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Infectious Diseases Unit, +39 0512143595, pierluigi.viale@unibo.it
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Scientific contact |
Prof. Pierluigi Viale, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Infectious Diseases Unit, +39 0512143595, pierluigi.viale@unibo.it
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Mar 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Sep 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the safety of pre-emptive therapy with Liposomal Amphotericin B (LamB) 5 mg/kg in the first 24h of treatment followed by LamB 3 mg/kg starting from the third day in patients with predefined high risk for invasive candidiasis (IC)//intra-abdominal candidiasis (IAC)
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Protection of trial subjects |
The protection of clinical trial subjects is consistent with the principles set out in the Declaration of Helsinki
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Nov 2019
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
1 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
20
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From 65 to 84 years |
20
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||
Pre-assignment
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Screening details |
Adult patients (≥ 18 years) with a severe surgical abdominal disease (SAD), defined as post-operative peritonitis, recurrent gastrointestinal perforation, post-operative hepatobiliary and pancreatic disorders, intra-abdominal abscess and anastomotic leak, and with severe sepsis or septic shock | ||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Arms
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Arm title
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Overall trial | ||||||
Arm description |
- | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Liposomal Amphotericin B (Ambisome)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
A loading dose of 5 mg/kg of L-AmB was administered on day 0. No antifungal therapy was given on days 1 and 2. On day 3, the decision to continue antifungal treatment at the standard dosage (3 mg/kg) was based on baseline serum 1,3-β-d-glucan (BG) levels (measured on day 0) and clinical criteria as follows:
If baseline BG was negative (<80 pg/mL) and the patient was clinically stable, antifungal therapy was discontinued.
If invasive candidiasis (IC) or intra- abdominal candidiasis (IAC) was confirmed by culture results, antifungal treatment continued at a dosage of 3 mg/kg every 24 hours for 7–14 days, as determined by the attending physician.
If baseline BG was significantly positive (>200 pg/mL) or IC/IAC was confirmed by culture results, antifungal treatment was continued for 7–14 days at the attending physician’s discretion.
If baseline BG was between 80 and 200 pg/mL, antifungal treatment continued at the standard dosage.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- |
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End point title |
Safety [1] | ||||||
End point description |
Tolerability of pulse high dose L-AmB as pre-emptive therapy in patients at high risk for intra-abdominal candidiasis
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End point type |
Primary
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End point timeframe |
Overall trial
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Since the primary endpoint focuses on the safety of the investigational product, no statistical analyses were conducted; instead, the frequency of adverse events in the enrolled population was reported. |
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No statistical analyses for this end point |
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End point title |
Incidence of invasive candidiasis | ||||||
End point description |
Number of patients with confirmed invasive intra-abdominal candidiasis
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End point type |
Secondary
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End point timeframe |
Overall trial
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Overall trial
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.1
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Reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
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Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: During the LAMBDA trial, six serious adverse events (SAE) and no serious adverse reactions (SARs) were reported to the Sponsor. All reported SAEs had a “fatal” outcome and no one of these was considered to be related to the investigational product. Therefore, no actions were taken for safety reasons, throughout the LAMBDA study. |
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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30 Aug 2021 |
Change from a multicenter study to a single-center study as the activation of other participating centers was never implemented.
Possibility to obtain informed consent to participate in the study/sub-study after the decision to include the subject in the clinical trial in emergency situations, in accordance with Article 35 of EU Regulation No. 536/2014, "Clinical trials in emergency situations".
Study duration modification.
An addendum was added to the protocol listing the expected Serious Adverse Events (SAEs) for the disease/population under study, for which expedited reporting within 24 hours is deemed unnecessary. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/37838147 |