NEWS HIGHLIGHTS
Published Studies Related to Mephyton (Phytonadione)
Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study. [2003.11.10]
BACKGROUND: Treatment of patients with excessive anticoagulation is routinely done by intravenous phytonadione (vitamin K1). Oral administration of phytonadione has been shown to be an effective alternative to the intravenous route, but these methods have never been compared directly. Our objective was to compare efficacy and safety of intravenous vs oral phytonadione treatment in patients with excessive anticoagulation without bleeding... CONCLUSION: Oral administration of phytonadione had similar efficacy and safety as intravenously administered phytonadione and may be suitable for treatment of patients with excessive anticoagulation.
Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation. [2000.10]
STUDY OBJECTIVE: To compare the efficacy of managing excessive anticoagulation in the absence of bleeding by either omitting warfarin therapy alone or administering oral phytonadione in addition to omitting warfarin therapy... CONCLUSION: The addition of oral phytonadione 2.5 mg reduced the time to achieve an INR of 4.0 by approximately 1 day compared with omitting warfarin therapy alone. Adverse events did not differ between the two groups. Both strategies were effective in managing asymptomatic patients with INRs of 6.0-10.0. Oral phytonadione may be most appropriate for patients at high risk for bleeding in whom the benefit of prompt INR reduction would outweigh the thromboembolic risk associated with INR overcorrection.
Time course of reversal of anticoagulant effect of warfarin by intravenous and subcutaneous phytonadione. [1999.12.13]
BACKGROUND: Excessive anticoagulation increases the risk of hemorrhagic complications associated with oral anticoagulant therapy. Oral or parenteral phytonadione is used to reverse excessive anticoagulation. Intravenous (IV) phytonadione, while effective, is associated with a small risk of serious anaphylactic reactions. Subcutaneous (SC) administration is safer, but there is little information on its relative efficacy in small doses... CONCLUSIONS: For patients who are excessively anticoagulated with warfarin, small doses of SC phytonadione may not correct the INR as rapidly or as effectively as when administered IV. Higher doses must be considered for more rapid and complete reversal of anticoagulation by the SC route.
Reversal of excessive effect of regular anticoagulation: low oral dose of phytonadione (vitamin K1) compared with warfarin discontinuation. [1993.10]
To determine the best way to reverse the excessive effect of regular anticoagulation in patients with INR > 5 and no bleeding complications, 23 patients with INR > 5 were randomly subdivided into two groups: group A (n = 12) discontinued warfarin for one day and group B (n = 11) received 2 mg of vitamin K1 orally in addition to the usual warfarin dose...
Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis. [2006.02.27]
BACKGROUND: Patients taking oral anticoagulants with an international normalized ratio (INR) greater than 4.0 are at increased risk for bleeding. We performed a meta-analysis to determine the effectiveness of phytonadione (vitamin K) in treating excessive anticoagulation... CONCLUSIONS: Limited evidence suggests that oral and intravenous vitamin K are equivalent and more effective for excessive anticoagulation than simply withholding warfarin sodium. Subcutaneous vitamin K, however, is inferior to oral and intravenous vitamin K for this indication and is similar to placebo. Whether treatment with vitamin K decreases hemorrhagic events cannot be determined from the published literature.
Clinical Trials Related to Mephyton (Phytonadione)
Low Dose Supplementation to Improve Anticoagulation Control With Oral Vitamin K as an Adjuvant to Warfarin Therapy [Recruiting]
The main objective of this study is to assess the effectiveness of low dose Vitamin K1 (200
micrograms per day) at improving anticoagulation control in unstable patients on warfarin.
This study will also aim to look at effectiveness in the context of genes known to influence
warfarin metabolism, variability in the consumption of Vitamin K rich foods, and patient
knowledge about warfarin anticoagulation - - factors which have been associated with
anticoagulation control and which can influence the effectiveness of this intervention in
clinical practice.
Comparing Different Routes and Doses of Phytonadione (Vitamin K) for Reversing Warfarin Treated Patients With Hip Fracture Before Surgery [Not yet recruiting]
It is well known that femoral neck fractures carry a significant increase in patients'
mortality and that surgical intervention is the preferred treatment.
Any delay in operating on such patients would inevitably increase their risk of developing
complications. One of the reasons for such unintentional delay would be the hypercoagulative
status of patients taking warfarin. The CHEST 2008 guidelines suggest reversing warfarin
with Vitamin K for patients who need urgent operation. The aim of this study is to compare
different roots and doses of Vitamin K.
Vitamin K Supplementation in Post-Menopausal Osteopenia [Active, not recruiting]
The purpose of this study is to determine whether supplementation with 5 mg vitamin K daily
over a 2-year period will prevent bone loss in post-menopausal women with osteopenia.
Oral Vitamin K for Warfarin Associated Coagulopathy [Active, not recruiting]
Excessive prolongation of the international normalized ratio (INR) occurs frequently in
patients taking warfarin; in fact, about one in six INR values is above the desired range.
Excessive prolongation of the INR is clinically important because the risk of bleeding
approximately doubles for each one point increase in the INR beyond the usual therapeutic
range. Thus, treatment strategies which rapidly and reliably lower an excessively prolonged
INR into the desired range have the potential to reduce bleeding. When taken by patients with
INR values between 4. 5 and 10, a small dose of oral vitamin K (1 mg to 2. 5mg) reduces the INR
into the desired INR range in about 75% of cases within 24 hours of its administration. If
warfarin is simply withheld, and no vitamin K is given, about 25% of patients will have an
INR in the desired range at 24 hours. However, vitamin K is rarely given to such patients. In
a recent survey carried out by our group, less than 20% of such patients would have been
given low dose oral vitamin K by a group of physicians who regularly supervise warfarin
therapy.
The most common treatment for excessive prolongation of the INR is to simply withhold
warfarin and allow the INR to fall into the therapeutic range. Although this strategy is
effective its safety has never been adequately examined. In fact, recent evidence suggests
that patients with INR values of more than 6. 0 who are treated with simple warfarin
withdrawal have a risk of major bleeding of 4% in the two weeks after they develop their
prolonged INR.
When asked why they did not give oral vitamin K to a non-bleeding patient who has an
excessively prolonged INR, physicians generally give one of three reasons: (1)They are not
convinced that oral vitamin K reduces bleeding. (2) They are concerned that oral vitamin K
may cause thrombosis. (3) In contrast with simply withholding warfarin, giving oral vitamin K
requires a patient to visit the physician, and the physician must have a supply of vitamin
K.
We hypothesize that the routine practice of not administering oral vitamin K to patients with
excessively prolonged INR values is causing patients to have major, life-threatening and
fatal bleeds. To convince physicians that oral vitamin K should be administered to all
non-bleeding patients with INR values of more than 4. 5, we propose a study which we
anticipate will demonstrate that oral vitamin K reduces bleeding, does not cause thrombosis,
and can be administered at home without direct physician supervision.
To accomplish these goals, we propose a multinational, double-blind, placebo-controlled
trial. We will randomize patients with INR values between 4. 5 and 10. 0 to receive 1. 25 mg of
oral vitamin K or placebo and follow them for bleeding and thrombosis. Patients with INR
values of more than 10. 0 will receive a single 1. 25 mg dose of oral vitamin K.
Successful completion of this study will establish a treatment standard supported by clinical
data which will, in turn, change the way that patients taking warfarin who present with an
excessively prolonged INR are treated.
Does Low Dose Oral Vitamin K Improve International Normalized Ratio (INR) Stability? [Not yet recruiting]
Warfarin is highly effective for the prevention of both first and recurrent thrombotic
events, however even minor excursions outside the reference INR range of 2. 0 to 3. 0 are
associated with bleeding or thrombotic complications. The importance of maintaining the INR
within the desired interval has led to the concept of "time in therapeutic range (TTR)" -
the total proportion of time that the INR is between 2. 0 and 3. 0. The investigators propose
a multicentre, double blind, randomized trial which will determine if 0. 150 mg of oral
vitamin K increases time in the therapeutic range for patients receiving warfarin.
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