Lessening Organ Dysfunction With VITamin C in Septic ARDS

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).

Conditions

• Septic
• Acute Respiratory Distress Syndrome

Interventions

DRUG

Administration of vitamin C

The intervention is intravenous vitamin C administered in bolus doses of 50 mg/kg mixed in a 50-mL solution of either dextrose 5% in water (D5W) or normal saline (0.9% NaCl), during 30 to 60 minutes or more for participants over 120 kg not to exceed 100 mg/minute, every 6 hours for 96 hours (i.e. 200 mg/kg/day and 16 doses in total). The other name of the drug: Ascorbic acid.

DRUG

Administration of placebo

Administration of placebo. Patients (in the control arm) will receive dextrose 5% in water (D5W) or normal saline (0.9% NaCl) in a volume to match the vitamin C. Placebo will be infused over 30 to 60 minutes or more for participants over 120 kg not to exceed 100 mg/minute as per the infusion instructions of vitamin C.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Djillali ANNANE, MD, PhD · Department Intensive Care Unit, Hospital Raymond Poincaré - APHP

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-07-22

Primary Completion

2024-07-31

Completion

2024-07-31

Countries

• France

Study Locations