SepticPhase 3LOVIT ARDSNCT04404387
Lessening Organ Dysfunction With VITamin C in Septic ARDS
A Phase 3 study testing Administration of vitamin C in people with Septic and Acute Respiratory Distress Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic, Acute Respiratory Distress Syndrome
- What is being tested?
- Administration of vitamin C
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 800 participants
- Where
- 1 siteFrance
- Study dates
- 22 Jul 2022to Jul 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- > 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;
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- 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).
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Department Intensive Care Unit, Hospital Raymond Poincaré - APHP
Garches, 92100
About this study
Official title: A Multicentre Concealed-Allocation Parallel-Group Blinded Randomized Controlled Trial to Ascertain the Effect of High-Dose Intravenous Vitamin C Compared to Placebo on Mortality or Persistent Organ Dysfunction at 28 Days in Septic Intensive Care Unit Patients
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:
Read more
- To compare the effect of high-dose intravenous vitamin C vs. placebo on:
- 6-month mortality;
- 6-month HRQoL;
- organ function (days 1, 2, 3, 4, 7, 10, 14, and 28 if in ICU);
- global tissue dysoxia (at baseline);
- 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);
- occurrence of stage 3 acute kidney injury as defined by KDIGO (Kidney Disease: Improving Global Outcomes) criteria20;
- 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;
- 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).
Read the detailed description
Treatment options for sepsis complicated by ARDS are limited to antimicrobials and supportive care (intravenous fluids, vasopressors, mechanical ventilation and renal replacement therapy). Recent preliminary evidence suggests that intravenous vitamin C may be the first therapy to mitigate the dysregulated cascade of events transforming an infection into sepsis. However, definitive practice changing evidence requires a large trial powered to detect a plausible, modest, and clinically important difference in mortality.
The study LOVIT will be conducted simultaneously in Canada (country of coordination), France, the United States of America, the United Kingdom and Australia/New Zealand.The data from each country will be merged with the aim of reaching 4,000 patients globally (roughly 800 patients per country). Thus, in the context of increasing off-label use of vitamin C for sepsis and ongoing trials of vitamin C bundled with other pharmacological interventions, this study will constitute a rigorous assessment of the effect of vitamin C monotherapy on patient-important outcomes. Moreover, the French LOVIT-ARDS, part of LOVIT, will provide additional information on the specific subgroup of patients with sepsis and ARDS.
This is a prospective multicentric randomized controlled trial. Web-based randomization system available 24/7. Eligible patients will be randomized in a 1:1 ratio to vitamin C or matching placebo. The study will use permuted blocks of undisclosed and variable size and stratify randomization by site.
The study will enroll a total of at least 770 patients. Sites are expected to enroll at least 1or 2 patients per month. By enrolling 385 evaluable patients per arm, the study will have 80% power to detect a 10% absolute risk reduction (from 50% to 40%, which corresponds to a 20% relative risk reduction).
Follow-up in the study for each patient: daily during ICU stay and telephone follow-up at 6 months.
- Conditions
- Septic, Acute Respiratory Distress Syndrome
- Being tested
- Administration of vitamin C, Administration of placebo
- Keywords
- Septic, Acute respiratory distress syndrome, Vitamin C
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Administration of vitamin CDrug
Also called Administration of Ascorbic acid
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.
Administration of placeboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | vitamin C 50 mg/kg every 6 hours for 96 hours. Receives: Drug: Administration of vitamin C |
| Control arm | Placebo comparator | Placebo administration Receives: Drug: Administration of placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Both assessed at 28 days
Secondary outcomes (7)
Vital statue at 6 months
Mortality at 6 months
Measured: at 6 months
Quality of life assessement: EQ-5D-5L
Quality of life of patients will be assessed by the questionnaire EQ-5D-5L.
The questionnaire EQ-5D-5L essentially consists of 2 pages:
- page1: the EQ-5D-5L descriptive system:
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box (1-digit number) next to the most appropriate statement in each of the five dimensions.
- page 2: the EQ visual analogue scale (VAS): the EQ VAS records the patient's self-rated health on a vertical visual analogue scale.
The 2 parts of the questionnaire can not be assessed seperately.
Measured: at 6 months
Daily organ function
Daily organ function (SOFA score days 1, 2, 3, 4, 7, 10, 14, and 28);
Measured: Days 1, 2, 3, 4, 7, 10, 14, 28
Global tissue dysoxia
Global tissue dysoxia: assessed by serum lactate concentration
Measured: At baseline and days 1, 3, 7
Occurrence of stage 3 acute kidney injury
Occurrence of stage 3 acute kidney injury as defined by KDIGO criteria
Measured: Up to day 28
Acute hemolysis
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;
- 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.
Measured: Up to day 28
Hypoglycemia
Hypoglycemia as defined by core lab-validated glucose levels of less than < 3.8 mmol/L.
Measured: During the time participants receive the 16 doses of the investigational product and the 7 days following the last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2020
- Study start22 Jul 2022
- Primary completionJul 2024 (estimated)
- Study completionJul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepticStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Djillali ANNANE, MD, PhD, Principal investigator, Department Intensive Care Unit, Hospital Raymond Poincaré - APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04404387
- Sponsor's protocol ID
- APHP200019
- Other IDs
- 2019-003350-80, 2020-003923-40, 2019
- Acronym
- LOVIT ARDS
- Status last verified
- Jan 2024
- First submitted
- 19 May 2020
- Last updated
- 31 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre Concealed-Allocation Parallel-Group Blinded Randomized Controlled Trial to Ascertain the Effect of High-Dose Intravenous Vitamin C Compared to Placebo on Mortality or Persistent Organ Dysfunction at 28 Days in Septic Intensive Care Unit Patients
- ClinicalTrials.gov ID
- NCT04404387
- Acronym / sponsor ID
- LOVIT ARDS / APHP200019
- Conditions
- Septic, Acute Respiratory Distress Syndrome
- Keywords
- Septic, Acute respiratory distress syndrome, Vitamin C
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 22 Jul 2022 (actual)
- Primary completion
- Jul 2024 (estimated)
- Study completion
- Jul 2024 (estimated)
- First posted
- 27 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 6-month mortality;
- 6-month HRQoL;
- organ function (days 1, 2, 3, 4, 7, 10, 14, and 28 if in ICU);
- global tissue dysoxia (at baseline);
- 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);
- occurrence of stage 3 acute kidney injury as defined by KDIGO (Kidney Disease: Improving Global Outcomes) criteria20;
- 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;
- 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).
Detailed description
Treatment options for sepsis complicated by ARDS are limited to antimicrobials and supportive care (intravenous fluids, vasopressors, mechanical ventilation and renal replacement therapy). Recent preliminary evidence suggests that intravenous vitamin C may be the first therapy to mitigate the dysregulated cascade of events transforming an infection into sepsis. However, definitive practice changing evidence requires a large trial powered to detect a plausible, modest, and clinically important difference in mortality.
The study LOVIT will be conducted simultaneously in Canada (country of coordination), France, the United States of America, the United Kingdom and Australia/New Zealand.The data from each country will be merged with the aim of reaching 4,000 patients globally (roughly 800 patients per country). Thus, in the context of increasing off-label use of vitamin C for sepsis and ongoing trials of vitamin C bundled with other pharmacological interventions, this study will constitute a rigorous assessment of the effect of vitamin C monotherapy on patient-important outcomes. Moreover, the French LOVIT-ARDS, part of LOVIT, will provide additional information on the specific subgroup of patients with sepsis and ARDS.
This is a prospective multicentric randomized controlled trial. Web-based randomization system available 24/7. Eligible patients will be randomized in a 1:1 ratio to vitamin C or matching placebo. The study will use permuted blocks of undisclosed and variable size and stratify randomization by site.
The study will enroll a total of at least 770 patients. Sites are expected to enroll at least 1or 2 patients per month. By enrolling 385 evaluable patients per arm, the study will have 80% power to detect a 10% absolute risk reduction (from 50% to 40%, which corresponds to a 20% relative risk reduction).
Follow-up in the study for each patient: daily during ICU stay and telephone follow-up at 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental arm | Experimental | Drug: Administration of vitamin Cvitamin C 50 mg/kg every 6 hours for 96 hours. |
| Control arm | Placebo comparator | Drug: Administration of placeboPlacebo administration |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- > 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Administration of vitamin CAlso: Administration of Ascorbic acidThe 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 | Experimental arm |
| Administration of placeboAdministration 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. | Drug | Control arm |
Primary outcome
Number of deceased participants or with persistent organ dysfunction
Time frame: Both assessed at 28 days
Defined as death or persistent organ dysfunction: continued dependency on mechanical ventilation, renal replacement therapy, or vasopressors.
7 secondary outcomes
Vital statue at 6 months
Time frame: at 6 months
Quality of life assessement: EQ-5D-5L
Time frame: at 6 months
Daily organ function
Time frame: Days 1, 2, 3, 4, 7, 10, 14, 28
Global tissue dysoxia
Time frame: At baseline and days 1, 3, 7
Occurrence of stage 3 acute kidney injury
Time frame: Up to day 28
Acute hemolysis
Time frame: Up to day 28
Hypoglycemia
Time frame: During the time participants receive the 16 doses of the investigational product and the 7 days following the last dose
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Djillali ANNANE, MD, PhD principal investigator
Department Intensive Care Unit, Hospital Raymond Poincaré - APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Administration of vitamin C in people with Septic and Acute Respiratory Distress Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 31 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Djillali ANNANE, MD, PhD (+33 1 47 10 77 87, djillali.annane@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of deceased participants or with persistent organ dysfunction (time frame: Both assessed at 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2024.