Study protocol for a randomized clinical trial to assess 7 versus 14-days of treatment for Pseudomonas aeruginosa bloodstream infections (SHORTEN-2 trial)
Copyright: © 2022 Molina et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..
BACKGROUND: Research priorities in Antimicrobial Stewardship (AMS) have rapidly evolved in the last decade. The need for a more efficient use of antimicrobials have fueled plenty of studies to define the optimal duration for antibiotic treatments, and yet, there still are large areas of uncertainty in common clinical scenarios. Pseudomonas aeruginosa has been pointed as a priority for clinical research, but it has been unattended by most randomized trials tackling the effectiveness of short treatments. The study protocol of the SHORTEN-2 trial is presented as a practical example of new ways to approach common obstacles for clinical research in AMS.
OBJECTIVE: To determine whether a 7-day course of antibiotics is superior to 14-day schemes for treating bloodstream infections by P. aeruginosa (BSI-PA).
METHODS: A superiority, open-label, randomized controlled trial will be performed across 30 Spanish hospitals. Adult patients with uncomplicated BSI-PA will be randomized to receive a 7 versus 14-day course of any active antibiotic. The primary endpoint will be the probability for the 7-day group of achieving better outcomes than the control group, assessing altogether clinical effectiveness, severe adverse events, and antibiotic exposure through a DOOR/RADAR analysis. Main secondary endpoints include treatment failure, BSI-PA relapses, and mortality. A superiority design was set for the primary endpoint and non-inferiority for treatment failure, resulting in a sample size of 304 patients.
CONCLUSIONS: SHORTEN-2 trial aligns with some of the priorities for clinical research in AMS. The implementation of several methodological innovations allowed overcoming common obstacles, like feasible sample sizes or measuring the clinical impact and unintended effects.
TRIAL REGISTRATION: EudraCt: 2021-003847-10; ClinicalTrials.gov: NCT05210439.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
PloS one - 17(2022), 12 vom: 10., Seite e0277333 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Molina, José [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Bacterial Agents |
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| Anmerkungen: |
Date Completed 26.12.2022 Date Revised 09.01.2023 published: Electronic-eCollection ClinicalTrials.gov: NCT05210439 EudraCT: 2021-003847-10 Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0277333 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM350597669 |
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| 245 | 1 | 0 | |a Study protocol for a randomized clinical trial to assess 7 versus 14-days of treatment for Pseudomonas aeruginosa bloodstream infections (SHORTEN-2 trial) |
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| 500 | |a Date Revised 09.01.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a ClinicalTrials.gov: NCT05210439 | ||
| 500 | |a EudraCT: 2021-003847-10 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright: © 2022 Molina et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||
| 520 | |a BACKGROUND: Research priorities in Antimicrobial Stewardship (AMS) have rapidly evolved in the last decade. The need for a more efficient use of antimicrobials have fueled plenty of studies to define the optimal duration for antibiotic treatments, and yet, there still are large areas of uncertainty in common clinical scenarios. Pseudomonas aeruginosa has been pointed as a priority for clinical research, but it has been unattended by most randomized trials tackling the effectiveness of short treatments. The study protocol of the SHORTEN-2 trial is presented as a practical example of new ways to approach common obstacles for clinical research in AMS | ||
| 520 | |a OBJECTIVE: To determine whether a 7-day course of antibiotics is superior to 14-day schemes for treating bloodstream infections by P. aeruginosa (BSI-PA) | ||
| 520 | |a METHODS: A superiority, open-label, randomized controlled trial will be performed across 30 Spanish hospitals. Adult patients with uncomplicated BSI-PA will be randomized to receive a 7 versus 14-day course of any active antibiotic. The primary endpoint will be the probability for the 7-day group of achieving better outcomes than the control group, assessing altogether clinical effectiveness, severe adverse events, and antibiotic exposure through a DOOR/RADAR analysis. Main secondary endpoints include treatment failure, BSI-PA relapses, and mortality. A superiority design was set for the primary endpoint and non-inferiority for treatment failure, resulting in a sample size of 304 patients | ||
| 520 | |a CONCLUSIONS: SHORTEN-2 trial aligns with some of the priorities for clinical research in AMS. The implementation of several methodological innovations allowed overcoming common obstacles, like feasible sample sizes or measuring the clinical impact and unintended effects | ||
| 520 | |a TRIAL REGISTRATION: EudraCt: 2021-003847-10; ClinicalTrials.gov: NCT05210439 | ||
| 650 | 4 | |a Clinical Trial Protocol | |
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Rosso-Fernández, Clara María |e verfasserin |4 aut | |
| 700 | 1 | |a Montero-Mateos, Enrique |e verfasserin |4 aut | |
| 700 | 1 | |a Paño-Pardo, José Ramón |e verfasserin |4 aut | |
| 700 | 1 | |a Solla, María |e verfasserin |4 aut | |
| 700 | 1 | |a Guisado-Gil, Ana Belén |e verfasserin |4 aut | |
| 700 | 1 | |a Álvarez-Marín, Rocío |e verfasserin |4 aut | |
| 700 | 1 | |a Pachón-Ibáñez, María Eugenia |e verfasserin |4 aut | |
| 700 | 1 | |a Gimeno, Adelina |e verfasserin |4 aut | |
| 700 | 1 | |a Martín-Gutiérrez, Guillermo |e verfasserin |4 aut | |
| 700 | 1 | |a Lepe, José Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Cisneros, José Miguel |e verfasserin |4 aut | |
| 700 | 0 | |a SHORTEN-2 trial team |e verfasserin |4 aut | |
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