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This study will randomize 20 septic shock patients to receive either a single 5 gram dose of IV vitamin B12 (Cyanokit® Meridian Medical Technologies, Columbia, MD) versus placebo in addition to standard of care to test the feasibility of completing clinical and laboratory protocols.
Following informed consent from patient's legally authorized representative, patients will be randomized to hydroxocobalamin or saline. Patients will have blood samples drawn up to 3 hours pre-dose and 3 hours post-dose to measure for hydrogen sulfide levels. Patients will also be followed for 3 hours after study drug infusion to monitor and record vasopressor dependence in norepinephrine-equivalent dose. Patients will then be followed through their medical record for 28 days to determine persistent organ dysfunction syndrome (PODS).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hydroxocobalamin | Experimental | Single IV infusion administered over a 10-15 minute period |
|
| Saline Placebo | Placebo Comparator | Single IV saline administered over a 10-15 minute period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydroxocobalamin | Drug | Single IV administration of Vitamin B12 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility of Clinical and Protocol Completion | Feasibility of completing clinical and laboratory protocols to the arm assigned | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Hydrogen Sulfide Concentration | Difference between pre- and post-dose hydrogen sulfide levels | 30 minutes post infusion |
| Persistent Organ Dysfunction Syndrome (PODS) | Prevalence of Persistent organ dysfunction syndrome (PODS) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jayshil J Patel, MD | Medical College of Wisconsin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26903338 | Background | Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287. | |
| 11700399 |
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20 patients from tertiary care medical and surgical intensive care units
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| ID | Title | Description |
|---|---|---|
| FG000 | Hydroxocobalamin | Single IV infusion administered over a 10-15 minute period |
| FG001 | Saline Placebo | Single IV saline administered over a 10-15 minute period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Critically ill adults with septic shock within 24 hours of ICU admission, randomized to a single 5-gram dose of IV hydroxocobalamin or equivalent volume 0.9% saline placebo
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| ID | Title | Description |
|---|---|---|
| BG000 | A Single 5-gram Dose of Hydroxocobalamin | Participants randomized to hydroxocobalamin received a single 5-gram IV infusion, administered over a 10-15-minute period |
| BG001 | Equivalent Volume 0.9% Saline Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Feasibility of Clinical and Protocol Completion | Feasibility of completing clinical and laboratory protocols to the arm assigned | critically ill adults with septic shock | Posted | Count of Participants | Participants | 28 days |
|
30 days
Serious adverse events were unexpected death and new acute kidney injury related to calcium oxalate nephropathy
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Hydroxocobalamin | Single IV infusion administered over a 10-15 minute period Hydroxocobalamin: Single IV administration of Vitamin B12 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jayshil Patel | Medical College of Wisconsin | 4149557042 | jpatel2@mcw.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 6, 2019 | Oct 15, 2025 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 6, 2019 | Oct 16, 2025 | SAP_003.pdf |
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| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
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| ID | Term |
|---|---|
| D006879 | Hydroxocobalamin |
| D014805 | Vitamin B 12 |
| D005947 | Glucose |
| ID | Term |
|---|---|
| D045728 | Corrinoids |
| D045725 | Tetrapyrroles |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 |
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Vitamin B12a is bright red and excreted in the urine. Due to this, patient allocation cannot be masked for patients or individuals who may care for them.
| Placebo | Drug | Single IV administration of saline |
|
|
| 28 days |
| Change in Vasopressor Dose | Vasopressor dose in mcg/kg/min (norepinephrine equivalents) | 3 hours |
| ICU Mortality | Intensive care unit mortality | during ICU stay, up to 30 days |
| Background |
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| 28778773 | Background | Zundel MT, Feih JT, Rinka JRG, Boettcher BT, Freed JK, Kaiser M, Ghadiali HY, Tawil JN, Woehlck HJ, Pagel PS. Hydroxocobalamin With or Without Methylene Blue May Improve Fluid Balance in Critically Ill Patients With Vasoplegic Syndrome After Cardiac Surgery: A Report of Two Cases. J Cardiothorac Vasc Anesth. 2018 Feb;32(1):452-457. doi: 10.1053/j.jvca.2017.04.002. Epub 2017 Apr 5. No abstract available. |
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| 36174744 | Derived | Patel JJ, Willoughby R, Peterson J, Carver T, Zelten J, Markiewicz A, Spiegelhoff K, Hipp LA, Canales B, Szabo A, Heyland DK, Stoppe C, Zielonka J, Freed JK. High-Dose IV Hydroxocobalamin (Vitamin B12) in Septic Shock: A Double-Blind, Allocation-Concealed, Placebo-Controlled Single-Center Pilot Randomized Controlled Trial (The Intravenous Hydroxocobalamin in Septic Shock Trial). Chest. 2023 Feb;163(2):303-312. doi: 10.1016/j.chest.2022.09.021. Epub 2022 Sep 26. |
Participants randomized to placebo received an equivalent volume 0.9% saline placebo, administered over a 10-15 minute period
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Norepinephrine equivalent dose at T0 | Median | Inter-Quartile Range | micrograms per kilogram per minute |
|
| SOFA score | unitless score with range 0-24 of severity of illness with higher score indicating greater severity of illness | Median | Inter-Quartile Range | units on a scale |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Hydrogen Sulfide Concentration | Difference between pre- and post-dose hydrogen sulfide levels | critically ill adults with septic shock | Posted | Mean | 95% Confidence Interval | micromolar | 30 minutes post infusion |
|
|
|
| Secondary | Persistent Organ Dysfunction Syndrome (PODS) | Prevalence of Persistent organ dysfunction syndrome (PODS) | critically ill adults with septic shock | Posted | Number | number of patients with PODS | 28 days |
|
|
|
| Secondary | Change in Vasopressor Dose | Vasopressor dose in mcg/kg/min (norepinephrine equivalents) | critically ill adults with septic shock | Posted | Median | Inter-Quartile Range | micrograms per kilogram per minute | 3 hours |
|
|
|
| Secondary | ICU Mortality | Intensive care unit mortality | Posted | Number | number of patients who died in the ICU | during ICU stay, up to 30 days |
|
|
|
| 4 |
| 10 |
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Saline Placebo | Single IV saline administered over a 10-15 minute period. Placebo: Single IV administration of saline | 4 | 10 | 0 | 10 | 0 | 10 |
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| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D006601 | Hexoses |
| D009005 | Monosaccharides |
| D000073893 | Sugars |
| D002241 | Carbohydrates |