Abstract | INTRODUCTION: METHODS AND ANALYSIS: This is a two-centre, phase I/II clinical trial. Phase I is a non-randomised dose-escalation study using a Bayesian optimal interval design in which up to 16 patients will be enrolled to evaluate the safest and most efficacious dose for stabilising cholesterol levels. Based on phase I results, the two best doses will be used to randomise 48 patients to either lipid injectable emulsion or active control (no treatment). Twenty-four patients will be randomised to one of two doses of the study drug, while 24 control group patients will receive no drug and will be followed during their hospitalisation. The control group will receive all standard treatments mandated by the institutional sepsis alert protocol. The phase II study will employ a permuted blocked randomisation technique, and the primary endpoint will be change in serum total cholesterol level (48 hours - enrolment). Secondary endpoints include change in cholesterol level from enrolment to 7 days, change in Sequential Organ Failure Assessment score over the first 48 hours and 7 days, in-hospital and 28-day mortality, lipid oxidation status, inflammatory biomarkers, and high-density lipoprotein function. ETHICS AND DISSEMINATION: Investigators are trained and follow good clinical practices, and each phase of the study was reviewed and approved by the institutional review boards of each institution. Results of each phase will be disseminated through presentations at national meetings and publication in peer-reviewed journals. If promising, data from the pilot study will be used for a larger, multicentre, phase II clinical trial. TRIAL REGISTRATION NUMBER: NCT03405870.
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Authors | Faheem W Guirgis, Lauren Page Black, Martin Daniel Rosenthal, Morgan Henson, Jason Ferreira, Christiaan Leeuwenburgh, Colleen Kalynych, Lyle L Moldawer, Taylor Miller, Lisa Jones, Marie Crandall, Srinivasa T Reddy, Samuel S Wu, Frederick A Moore |
Journal | BMJ open
(BMJ Open)
Vol. 9
Issue 9
Pg. e029348
(09 18 2019)
ISSN: 2044-6055 [Electronic] England |
PMID | 31537565
(Publication Type: Clinical Trial Protocol, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. |
Chemical References |
- Fat Emulsions, Intravenous
- Cholesterol
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Topics |
- Cholesterol
(blood)
- Clinical Trials, Phase I as Topic
- Clinical Trials, Phase II as Topic
- Fat Emulsions, Intravenous
(therapeutic use)
- Humans
- Sepsis
(blood, therapy)
- Shock, Septic
(blood, therapy)
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