Multiple Organ FailurePhase 4NCT02455180
Pharmacokinetics of Two Different High-dose Regimens of Intravenous Vitamin C in Critically Ill Patients
A Phase 4 study testing Ascorbic Acid in people with Multiple Organ Failure and Sepsis, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
The purpose of this study is to determine the pharmacokinetic properties of two different dosage regimens of intravenous vitamin C in patients admitted to the Intensive Care Unit with life-threatening illness. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Organ Failure, Sepsis, Systemic Inflammatory Response Syndrome
- What is being tested?
- Ascorbic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2015to Nov 2016
- Phase
- Phase 4
- 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
- Sepsis or Systemic Inflammatory Response Syndrome (SIRS) after major surgery or trauma;
- Non-neurological sequential organ failure assessment (SOFA) score >6;
- Expected length of ICU stay > 96 hours;
- Written proxy consent by legal representative.
Who cannot join
- Admission after out of hospital cardiac arrest
- Prior use of supplemental vitamin C in the week before
- Major bleeding
- Pre-existent renal insufficiency defined as an eGFR of < 30 ml/min/1.73 m2 (stadium 4-5)
- Expected need for renal replacement therapy within 48 hours
- Known glucose 6-phosphate dehydrogenase deficiency
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- History of urolithiasis or oxalate nephropathy
- Previous use of prolonged high dose vitamin C supplements
- Hemochromatosis
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine the pharmacokinetic properties of two different dosage regimens of intravenous vitamin C in patients admitted to the Intensive Care Unit with life-threatening illness.
Read the detailed description
Rationale:
Critically ill patients with trauma or sepsis exhibit a high degree of vitamin C deficiency at ICU admission and vitamin C plasma concentrations decrease even more during the first three days of admission. Vitamin C is a natural anti-oxidant and crucial for endothelial and organ protection
Objective:
To determine the pharmacokinetics of two high dose regimens of intravenous vitamin C in critically ill patients, in particular the attained plasma concentration and the fraction retained in the body and excreted in urine.
Study design:
Prospective randomized controlled pharmacokinetic intervention study
Study population:
Adult critically ill patients admitted to the ICU of the VU University Medical Center, Amsterdam, with sepsis or SIRS after major surgery or trauma with a non-neurological sequential organ failure (SOFA) score >6 and an expected length of ICU stay of >96 hours.
Intervention (if applicable):
Patients will receive either 2 or 10 gram/day vitamin C intravenously twice daily for two days in bolus or continuous infusion.
- Being tested
- Ascorbic Acid
- Keywords
- Critical Care
- Medical subject headings
- Multiple Organ Failure, Sepsis, Systemic Inflammatory Response Syndrome, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ascorbic AcidDrug
Also called Vitamin C
Patients receive vitamin C 4 times in either high (5g) or moderate (1g) dose. Vitamin C will be administered intravenously (ascorbinezuur CF 100 mg/ml, Centrafarm BV, Etten Leur, Netherlands) in 50ml of NaCl 0.9%, infused over 30 minutes.
| Study group | Role | What they receive |
|---|---|---|
| 4x 1 gram bolus (q12H) dosage regimen | Experimental | 1 gram of intravenous Vitamin C (ascorbic acid) is given 4 times at 12 hour intervals (total dose 4 grams). Receives: Drug: Ascorbic Acid |
| 4x 5 grams bolus (q12H) dosage regimen | Experimental | 5 grams of intravenous Vitamin C (ascorbic acid) is given 4 times at 12 hour intervals (total dose 20 grams). Receives: Drug: Ascorbic Acid |
| 4 gram continuous dosage regimen | Experimental | 1 gram per 12 hours of intravenous Vitamin C (ascorbic acid) is given continuously for 48 hours Receives: Drug: Ascorbic Acid |
| 20 gram continuous dosage regimen | Experimental | 5 gram per 12 hours of intravenous Vitamin C (ascorbic acid) is given continuously for 48 hours Receives: Drug: Ascorbic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vitamin C plasma concentration
Measured: Baseline (before intervention), thereafter at 1, 2, 4, 8, 12, 24, 36, 48, 72, 96 hours after first intervention
Vitamin C excreted in urine
Measured: 0-12hours after first intervention; 36-48 hours after first intervention
Secondary outcomes (7)
Oxalate excretion in urine
Measured: 0-12hours after first intervention; 36-48 hours after first intervention
F2-isoprostanes (oxidative damage biomarker)
Measured: 0, 24 and 72 hours after first intervention
CellROX (reactive oxygen species activity in leukocytes)
Measured: 0 and 24 hours after first intervention
Vasopressor requirements (noradrenalin dose)
Measured: 0, 12, 24, 48, 72 and 96 hours after first intervention
Renal resistive index (ultrasonography)
Measured: 0, 4, 24, 72 hours after first intervention
Serum creatinine and creatinine clearance
Measured: 0, 24, 48, 72, 95 after first intervention
Sequential Organ Failure Assessment (SOFA) score
Measured: 0, 24, 48, 72, 95 after first intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2015 (estimated)
- Study startMar 2015
- Primary completionOct 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple Organ FailureStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, H.M. Oudemans-van Straaten, MD, PhD, Amsterdam UMC, location VUmc
- Investigators
- H.M. Oudemans-van Straaten, MD, PhD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02455180
- Sponsor's protocol ID
- NL50578.029.14
- Other IDs
- 2014-003680-38, 2014
- Status last verified
- Aug 2017
- First submitted
- 21 May 2015
- Last updated
- 2 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
de Grooth HJ, Manubulu-Choo WP, Zandvliet AS, Spoelstra-de Man AME, Girbes AR, Swart EL, Oudemans-van Straaten HM. Vitamin C Pharmacokinetics in Critically Ill Patients: A Randomized Trial of Four IV Regimens. Chest. 2018 Jun;153(6):1368-1377. doi: 10.1016/j.chest.2018.02.025. Epub 2018 Mar 6.
PubMed 29522710
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Two Different High-dose Regimens of Intravenous Vitamin C in Critically Ill Patients
- ClinicalTrials.gov ID
- NCT02455180
- Acronym / sponsor ID
- NL50578.029.14
- Keywords
- Critical Care
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- Oct 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 27 May 2015 (estimated)
- 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 purpose of this study is to determine the pharmacokinetic properties of two different dosage regimens of intravenous vitamin C in patients admitted to the Intensive Care Unit with life-threatening illness.
Detailed description
Rationale:
Critically ill patients with trauma or sepsis exhibit a high degree of vitamin C deficiency at ICU admission and vitamin C plasma concentrations decrease even more during the first three days of admission. Vitamin C is a natural anti-oxidant and crucial for endothelial and organ protection
Objective:
To determine the pharmacokinetics of two high dose regimens of intravenous vitamin C in critically ill patients, in particular the attained plasma concentration and the fraction retained in the body and excreted in urine.
Study design:
Prospective randomized controlled pharmacokinetic intervention study
Study population:
Adult critically ill patients admitted to the ICU of the VU University Medical Center, Amsterdam, with sepsis or SIRS after major surgery or trauma with a non-neurological sequential organ failure (SOFA) score >6 and an expected length of ICU stay of >96 hours.
Intervention (if applicable):
Patients will receive either 2 or 10 gram/day vitamin C intravenously twice daily for two days in bolus or continuous infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 4x 1 gram bolus (q12H) dosage regimen | Experimental | Drug: Ascorbic Acid1 gram of intravenous Vitamin C (ascorbic acid) is given 4 times at 12 hour intervals (total dose 4 grams). |
| 4x 5 grams bolus (q12H) dosage regimen | Experimental | Drug: Ascorbic Acid5 grams of intravenous Vitamin C (ascorbic acid) is given 4 times at 12 hour intervals (total dose 20 grams). |
| 4 gram continuous dosage regimen | Experimental | Drug: Ascorbic Acid1 gram per 12 hours of intravenous Vitamin C (ascorbic acid) is given continuously for 48 hours |
| 20 gram continuous dosage regimen | Experimental | Drug: Ascorbic Acid5 gram per 12 hours of intravenous Vitamin C (ascorbic acid) is given continuously for 48 hours |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Sepsis or Systemic Inflammatory Response Syndrome (SIRS) after major surgery or trauma;
- Non-neurological sequential organ failure assessment (SOFA) score >6;
- Expected length of ICU stay > 96 hours;
- Written proxy consent by legal representative.
Key exclusion criteria (9 listed)
- Admission after out of hospital cardiac arrest
- Prior use of supplemental vitamin C in the week before
- Major bleeding
- Pre-existent renal insufficiency defined as an eGFR of < 30 ml/min/1.73 m2 (stadium 4-5)
- Expected need for renal replacement therapy within 48 hours
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 |
|---|---|---|
| Ascorbic AcidAlso: Vitamin CPatients receive vitamin C 4 times in either high (5g) or moderate (1g) dose. Vitamin C will be administered intravenously (ascorbinezuur CF 100 mg/ml, Centrafarm BV, Etten Leur, Netherlands) in 50ml of NaCl 0.9%, infused over 30 minutes. | Drug | 20 gram continuous dosage regimen, 4 gram continuous dosage regimen, 4x 1 gram bolus (q12H) dosage regimen, 4x 5 grams bolus (q12H) dosage regimen |
Primary outcome
Vitamin C plasma concentration
Time frame: Baseline (before intervention), thereafter at 1, 2, 4, 8, 12, 24, 36, 48, 72, 96 hours after first intervention
Vitamin C excreted in urine
Time frame: 0-12hours after first intervention; 36-48 hours after first intervention
7 secondary outcomes
Oxalate excretion in urine
Time frame: 0-12hours after first intervention; 36-48 hours after first intervention
F2-isoprostanes (oxidative damage biomarker)
Time frame: 0, 24 and 72 hours after first intervention
CellROX (reactive oxygen species activity in leukocytes)
Time frame: 0 and 24 hours after first intervention
Vasopressor requirements (noradrenalin dose)
Time frame: 0, 12, 24, 48, 72 and 96 hours after first intervention
Renal resistive index (ultrasonography)
Time frame: 0, 4, 24, 72 hours after first intervention
Serum creatinine and creatinine clearance
Time frame: 0, 24, 48, 72, 95 after first intervention
Sequential Organ Failure Assessment (SOFA) score
Time frame: 0, 24, 48, 72, 95 after first intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2017.
- Derived from this study: PubMed 29522710de Grooth HJ, Manubulu-Choo WP, Zandvliet AS, Spoelstra-de Man AME, Girbes AR, Swart EL, Oudemans-van Straaten HM. Vitamin C Pharmacokinetics in Critically Ill Patients: A Randomized Trial of Four IV Regimens. Chest. 2018 Jun;153(6):1368-1377. doi: 10.1016/j.chest.2018.02.025. Epub 2018 Mar 6.
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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.
H.M. Oudemans-van Straaten, MD, PhD principal investigator
Amsterdam UMC, location VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ascorbic Acid in people with Multiple Organ Failure and Sepsis, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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 4 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: finished, as of the sponsor's last update on 2 Aug 2017. 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 Netherlands. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vitamin C plasma concentration (time frame: Baseline (before intervention), thereafter at 1, 2, 4, 8, 12, 24, 36, 48, 72, 96 hours after first intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02455180, which also lists 1 linked publication.
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 2 Aug 2017.