CompletedNot Applicable

Randomized Controlled Clinical Trial to Investigate Effects of Vitamin K2 in COVID-19

Netherlands40 participantsStarted 2021-02-22

Plain-language summary

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.

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * COVID-19 patients who are admitted to the CWZ with COVID-19, with a laboratory confirmed SARS-CoV-2 infection within the previous 96 hours * Respiratory failure requiring supplemental oxygen, defined as requiring supplemental oxygen to sustain an arterial PO2 ≥70mmHg (measured by arterial blood gas) or an oxygen saturation of ≥94% (measured using a pulse oximeter) * At least 18 years old * Able to safely swallow the study medication or possibility of safely administering this through a nasogastric tube * Use of prophylactic heparin or LWMH according to hospital protocols, or use of therapeutic dosages if there is a medical indication for this * Informed consent signed by patient Exclusion Criteria: * Use of oral anticoagulation drugs; patients may be included when they have been switched to LMWH * Patients on vitamin K antagonists with a supra-therapeutic anticoagulation at admission who require vitamin K supplementation to correct this, or were administered vitamin K for this reason within the preceding 5 days * Patients already using vitamin K supplements at admission * Participation in another intervention study * Direct admission to an intensive care unit (ICU) for invasive ventilation at presentation * Confirmed active pulmonary embolism or deep venous thrombosis prior to inclusion * Known allergy to any of the components of the study medication or placebo * Patients who are hemodialysis dependent at admission * Pregnancy at the time of inclusion…

What they're measuring

Plasma desmosine levels

Timeframe: Day 1 until day 28 or until discharge if this is earlier.

Plasma dp-ucMGP levels

Timeframe: Day 1 until day 28 or until discharge if this is earlier.

Trial details

NCT IDNCT04770740

SponsorCanisius-Wilhelmina Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2022-03-01