Randomized Controlled Clinical Trial to Investigate Effects of Vitamin K2 in COVID-19 (KOVIT)
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|ClinicalTrials.gov Identifier: NCT04770740|
Recruitment Status : Recruiting
First Posted : February 25, 2021
Last Update Posted : March 3, 2021
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While the majority of people recover after mild symptoms, a portion of COVID-19 patients develops respiratory failure. Coagulopathy and thromboembolism are prevalent in severe COVID-19, and these factors are associated with decreased survival. Coagulation is an intricate balance between clot promoting and dissolving processes in which vitamin K plays an essential role. Elastin is a major component of dynamic tissues such as lungs and arteries, and elastin calcification stimulates elastin degradation and vice versa. The vitamin K-dependent Matrix Gla Protein (MGP) protects elastin from both calcification and degradation.
Although technically feasible, direct quantification of blood vitamin K levels is not an appropriate method to assess overall vitamin K status due to differences in bioavailability and half-life time between the two naturally occurring vitamin K forms (vitamin K1 and K2). Measuring inactive levels of vitamin K-dependent proteins in the circulation is the method recommended by most experts, as it represents the systemic availability of both vitamin K1 and K2. Dp-uc (dephospho uncarboxylated, i.e. inactive) MGP and proteins induced by vitamin K absence (PIVKA-II) both inversely correlate with vitamin K status and can be used as surrogate markers of total vitamin K status.
Recently, we found a severely reduced vitamin K status (as quantified by dp-ucMGP) in COVID-19 patients compared to controls. In COVID-19 patients, low vitamin K status was also associated with poor outcome (defined as the need for invasive ventilation or death), accelerated elastin degradation (quantified by plasma (iso)desmosine (DES) a byproduct of elastin degradation). Based on these finding and previous studies, we hypothesize that improving vitamin K-status by vitamin K supplementation could have favorable effects on pulmonary damage and coagulopathy in COVID-19.
|Condition or disease||Intervention/treatment||Phase|
|Covid19||Dietary Supplement: Vitamin K2 in the form of Menaquinone-7 (MK-7) Dietary Supplement: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||double blind, randomized, placebo-controlled|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase 2, Double Blind, Randomized, Placebo-controlled Clinical Trial to Investigate the Safety and Effects of Oral Vitamin K2 Supplementation in COVID-19|
|Actual Study Start Date :||February 22, 2021|
|Estimated Primary Completion Date :||June 1, 2021|
|Estimated Study Completion Date :||October 1, 2021|
Active Comparator: Experimental: Vitamin K2
Patients with COVID-19 who get our dietary supplement vitamin K2, three tablets of 333mcg a day, for 14 days or until discharge, whichever occurs earlier.
Dietary Supplement: Vitamin K2 in the form of Menaquinone-7 (MK-7)
Patients will take three tablets of vitamin K2 menaquinone-7 (333mcg) per day. Patients taking vitamin K2 MK-7 will receive the total of 999mcg per day from day 1 until day 14 or discharge, whichever occurs earlier. All subjects can be treated with prophylactic or therapeutic heparin-based (heparin or any low-molecular weight heparin) anticoagulants, according to local hospital protocols. Provided by Kappa Bioscience.
Placebo Comparator: Control: Placebo
Patients with COVID-19 who get placebo as control, three tablets a day, for 14 days or until discharge, whichever occurs earlier.
Dietary Supplement: Placebo
Patients will take three tablets of placebo containing only inactive ingredients per day, from day 1 until day 14 or until discharge, whichever occurs first. The placebo is provided by Kappa Bioscience.
- Plasma desmosine levels [ Time Frame: Day 1 until day 28 or until discharge if this is earlier. ]Plasma desmosine levels before and during vitamin K supplementation in intervention versus control patients.
- Plasma dp-ucMGP levels [ Time Frame: Day 1 until day 28 or until discharge if this is earlier. ]Plasma dp-uc MGP levels before and during vitamin K supplementation within the intervention group and in intervention versus control patients.
- Safety [ Time Frame: Day 1 until day 28 ]Difference between the number of grade 3 and grade 4 adverse events between the intervention and control group during treatment, with special attention for: progression of respiratory insufficiency, thrombotic events, pulmonary embolism or deep venous thrombosis, bleeding, renal insufficiency, cardiac decompensation, liver enzyme abdnormalities and/or liver failure.
- Serum PIVKA-II levels [ Time Frame: Day 1 until day 28 or until discharge if this is earlier. ]Serum PIVKA-II levels before and during vitamin K supplementation in intervention versus control patients.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04770740
|Contact: Margot Visser, M.D.||email@example.com|
|Contact: Jona Walk, M.D. PhDfirstname.lastname@example.org|
|Principal Investigator:||A. Dofferhoff, M.D. PhD||Canisius-Wilhelmina Hospital|