Lessening Organ Dysfunction With VITamin C in Septic ARDS

NCT04404387 | Unknown Phase 3 DMC

• 3 other identifiers: APHP2000192019-003350-802020-003923-40
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 1

Brief 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:

• 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;
• 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

Keywords

Septic; Acute respiratory distress syndrome; Vitamin C

Outcome Measures

Primary Outcomes (1)

• Number of deceased participants or with persistent organ dysfunction

  Defined as death or persistent organ dysfunction: continued dependency on mechanical ventilation, renal replacement therapy, or vasopressors.

  Both assessed at 28 days

Secondary Outcomes (7)

• Vital statue at 6 months

  at 6 months

• Quality of life assessement: EQ-5D-5L

  at 6 months

• Daily organ function

  Days 1, 2, 3, 4, 7, 10, 14, 28

• Global tissue dysoxia

  At baseline and days 1, 3, 7

• Occurrence of stage 3 acute kidney injury

  Up to day 28

Study Arms (2)

Experimental arm

EXPERIMENTAL

vitamin C 50 mg/kg every 6 hours for 96 hours.

Drug: Administration of vitamin C

Control arm

PLACEBO COMPARATOR

Placebo administration

Drug: Administration of placebo

Interventions

Administration of vitamin C DRUG

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.

Also known as: Administration of Ascorbic acid

Experimental arm

Administration of placebo DRUG

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.

Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• \> 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).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Department Intensive Care Unit, Hospital Raymond Poincaré - APHP

Garches, 92100, France

RECRUITING

MeSH Terms

Conditions

Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Djillali ANNANE, MD, PhD

  Department Intensive Care Unit, Hospital Raymond Poincaré - APHP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Djillali ANNANE, MD, PhD

CONTACT

+33 1 47 10 77 87; djillali.annane@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 27, 2020
• Study Start: July 22, 2022
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: January 31, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)