Efficacy of Para-Tyrosine Supplementation on the Survival and Clinical Outcome in Patients With Sepsis
NCT ID: NCT03278730
Last Updated: 2025-03-30
Study Results
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Basic Information
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SUSPENDED
PHASE2
296 participants
INTERVENTIONAL
2027-01-31
2027-02-28
Brief Summary
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Detailed Description
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The hypothesis of the study is, that supplementation of para-Tyrosine (p-Tyr) in the early phase of sepsis may diminish some specific inflammatory procedures and thus may have a favourable impact on the disease progress, and consequently on the mortality.
The primary objective of the study is to evaluate, whether oral P-Tyr supplementation reduces mortality compared to placebo group during the ICU stay in patients with sepsis.
The primary endpoint is the comparison of mortality starting from randomization and start of treatment (which should be on the same day) during the period of ICU stay between the active treatment group and placebo group. The secondary objectives of the study are:
to evaluate whether supplementation of p-Tyr has effect on clinical outcome of sepsis compared to placebo in patients receiving appropriate standard care; to evaluate the effect of p-Tyr supplementation on 28-day survival of patients with sepsis; to evaluate, whether the treatment can reduce the time of the ICU stay, to evaluate the effect on overall mortality of patients with sepsis during their hospitalization, to evaluate the effect of p-Tyr supplemetation on the overall hospitalization time, to evaluate the safety of the investigational product. The investigators wish to explore To explore whether serum level of p-Tyr can be maintained with the oral supplementation; dynamics and interrelation of the levels of oxidative stress markers (o- and m-Tyr) and the physiologic isomer of Tyr (p-Tyr) and Phenylalanine (Phe) and the correlation of o-Tyr and m-Tyr serum levels and other parameters of inflammation.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
QUADRUPLE
Study Groups
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Para-Tyrosine intervention
The patients will receive the study drug during their stay at the ICU but for a maximum of 7 days.
Study drug will be dispensed by a nominated member of the study team and administered to the patients by the ICU staff via nasogastric tube in form of oral suspension. The content of the hard capsules will be dissolved in 20 ml of tap water before the dosing.
Drug name: Tyrosine. Strength 500 mg. Oral dose form: hard capsule. Number of Dispensed at frequency of 3x2 g daily. Duration of administration: 4 to 7 days.
Para-Tyrosine supplementation
Patients will recieve the study drug during their stay at the ICU, but for a maximum of 7 days. The study drug is 3x2 gramms of para-Tyrosine, which will be dispensed and administered in a form of oral suspension via a nasogastric tube.
Placebo
The patients will receive the study drug during their stay at the ICU but for a maximum of 7 days.
Study drug will be dispensed by a nominated member of the study team and administered to the patients by the ICU staff via nasogastric tube in form of oral suspension. The content of the hard capsules will be dissolved in 20 ml of tap water before the dosing.
Drug name: Placebo.. Strength N/A. Oral dose form: capsule matching to Tyrosine capsule. Number of Dispnsed an frequency 3x2 g daily. Duration of administration: 4 to 7 days.
Placebo solution
Patients will recieveplacebo during their stay at the ICU, but for a maximum of 7 days. The study drug is 3x2 gramms of placebo, which will be dispensed and administered in a form of oral suspension via a nasogastric tube.
Interventions
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Para-Tyrosine supplementation
Patients will recieve the study drug during their stay at the ICU, but for a maximum of 7 days. The study drug is 3x2 gramms of para-Tyrosine, which will be dispensed and administered in a form of oral suspension via a nasogastric tube.
Placebo solution
Patients will recieveplacebo during their stay at the ICU, but for a maximum of 7 days. The study drug is 3x2 gramms of placebo, which will be dispensed and administered in a form of oral suspension via a nasogastric tube.
Eligibility Criteria
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Inclusion Criteria
2. Male and female patients ≥ 18 years
3. Have a current primary diagnosis of sepsis based on the the third international consensus definitions for sepsis and septic shock (Sepsis-3)Willing and able to comply with all aspects of the protocol
4. Females of childbearing potential must have negtive serum pregnancy test az screening. (All females will be considered to be of childbearing potential unless they are postmenopausal i.e. amenorrheic for at least 12 consecutive months, in the appropriate age group and without other known or suspected cause or have been sterilized surgically i.e. bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
Exclusion Criteria
1. Females who are pregnant (positive β-hCG test at screening) or breastfeeding
2. chronic use of steroids or immunosuppressive drugs within the past 3 months
3. other therapy influencing the immune system within the past 3 months (radiotherapy, chemotherapy etc.)
4. malignant hematologic disease
5. jejunal tube feeding
6. any other significant illness in the medical history ongoing in the preceeding 1 month, which may have an influence on the survival and clinical outcome of the patients (e.g severe chronic heart failure NYHA III-IV., AMI, stroke, major surgery, COPD, renal failure, hepatic failure, hepatic cirrhosis etc.)
7. Life expectancy less, than 1 months according to the judgement of the Investigator (even without significant illness, due to age or general status of the patient)
8. Hypersensitivity to any of the excipients of the study product
9. Known to be human immunodeficiency virus (HIV) positive
10. Active viral hepatitis (B or C) as demonstrated by positive serology
11. History of drug or alcohol dependency or abuse within approximately the last 2 years
18 Years
ALL
No
Sponsors
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University of Pecs
OTHER
Responsible Party
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István Wittmann
Professor
Principal Investigators
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István Wittmann, MD,PhD,DSc
Role: PRINCIPAL_INVESTIGATOR
University of Pecs
Locations
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2nd Department of Medicine and Nephrological Center
Pécs, Baranya, Hungary
Department of Anaesthesiology and Intensive Care
Pécs, Baranya, Hungary
Countries
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References
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Kun S, Molnar GA, Selley E, Szelig L, Bogar L, Csontos C, Miseta A, Wittmann I. Insulin Therapy of Nondiabetic Septic Patients Is Predicted by para-Tyrosine/Phenylalanine Ratio and by Hydroxyl Radical-Derived Products of Phenylalanine. Oxid Med Cell Longev. 2015;2015:839748. doi: 10.1155/2015/839748. Epub 2015 Oct 20.
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Molnar GA, Nemes V, Biro Z, Ludany A, Wagner Z, Wittmann I. Accumulation of the hydroxyl free radical markers meta-, ortho-tyrosine and DOPA in cataractous lenses is accompanied by a lower protein and phenylalanine content of the water-soluble phase. Free Radic Res. 2005 Dec;39(12):1359-66. doi: 10.1080/10715760500307107.
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Other Identifiers
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PTE-2015-02
Identifier Type: -
Identifier Source: org_study_id
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