Lessening Organ Dysfunction With VITamin C in Septic ARDS

• Status: Not yet recruiting
• Trial end date: 2023-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of the study aims to compare the effect of high-dose intravenous vitamin C vs. placebo on a composite of death or persistent organ dysfunction - defined as continued dependency on mechanical ventilation, new renal replacement therapy, or vasopressors - assessed at 28 days on intensive care unit (ICU) patients.

As secondary objectives, the study aims:

• To compare the effect of high-dose intravenous vitamin C vs. placebo on:

1. 6-month mortality;

2. 6-month HRQoL;

3. organ function (days 1, 2, 3, 4, 7, 10, 14, and 28 if in ICU);

4. global tissue dysoxia (at baseline);

5. oxygenation Index (FiO2 x Mean Airway Pressure/PaO2) (days 1, 2, 3, 4, 7, 10, 14, and 28 if in ICU, and if still intubated);

6. occurrence of stage 3 acute kidney injury as defined by KDIGO (Kidney Disease:

Improving Global Outcomes) criteria20;

7. acute hemolysis as defined by:

• clinician judgment of hemolysis, as recorded in the chart, or

• hemoglobin drop of at least 25 g/L within 24 hours of a dose of investigational product PLUS 2 of the following:

• reticulocyte count >2 times upper limit of normal at clinical site lab;

• haptoglobin < lower limit of normal at clinical site lab;

• indirect (unconjugated) bilirubin >2 times upper limit of normal at clinical site lab;

• lactate dehydrogenase (LDH) >2 times upper limit of normal at clinical site lab.

Severe hemolysis:

• hemoglobin < 75 g/L AND at least 2 of the above criteria AND requires 2 units of packed red blood cells;

8. hypoglycemia as defined as core lab-validated glucose levels of less than < 3.8 mmol/L.

• To assess baseline vitamin C levels in study participants (before the first dose of investigational product).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Ascorbic Acid

Criteria

Inclusion Criteria:

• Patients ≥18 years;

• Admitted to ICU with proven or suspected infection as the main diagnosis;

• Currently treated with a continuous intravenous infusion of vasopressors (norepinephrine, epinephrine, vasopressin, dopamine, phenylephrine);

• Presenting with Acute Respiratory Distress Syndrome

• Patient who has signed an informed and written consent, whenever he/she is capable of consent, if not ascent from his/her representant whenever he/she is present at time of screening for inclusion

• Affiliation to a social security system or to an universal health coverage (Couverture Maladie Universelle, CMU).

• Patients under guardianship or curatorship will be included.

• Patients in case of simple emergency (legal definition) will be included.

Exclusion Criteria:

• > 24 hours of intensive care unit (ICU) admission;

• Known Glucose-6-phosphate dehydrogenase (G6PD) deficiency;

• Pregnancy;

• Known allergy to vitamin C;

• Known kidney stones within the past 1 year;

• Received any intravenous vitamin C during this hospitalization unless incorporated in parenteral nutrition;

• Expected death or withdrawal of life-sustaining treatments within 48 hours;

• Previously enrolled in this study;

• Previously enrolled in a trial for which co-enrolment is not allowed (co-enrolment to be determined case by case).