Clinical trials venous thrombosis

It is remarkable that most of the data collected from the available SERMs are unanimous in reproducing an estrogen agonistic profile in venous thrombogenesis. The vast clinical experience acquired with tamoxifen confirms an augmented risk for both deep venous thrombosis and pulmonary embolism. This increase, however, did not presuppose increased mortality in the overview of randomized trials of adjuvant tamoxifen for early breast cancer, where the one extra death per 5000 woman-years of tamoxifen attributed to pulmonary embolus was not statistically significant (Early Breast Cancer Trialists Collaborative Group 1998). 

Recombinant human erythropoietin (rHuEpo) may increase the risk of thrombosis (201). It has been reported that patients with carcinoma of the cervix who received chemotherapy and rHuEpo have an increased risk of symptomatic venous thrombosis (201). In clinical trials where the maintenance hematocrit was 3% on PROCRIT clotting of the arteriovenous shunts occurred at an annual rate of about 0.25 events per patient per year. However, other thrombotic conditions such as cerebrovascular events, transient ischemic attacks, myocardial infarction, or pulmonary embolism occurred at a rate of 0,04 events per patient per year (202). In a separate study of I, I I I untreated patients on hemodialysis, clotting of arteriovenous shunts occurred at a rate of 0.5 events per patient per year. In patients with chronic renal failure on hemodialysis who also had congestive heart failure, ischemic heart disease and venous thrombosis were increased in patients who were treated with PROCRIT targeted to a hematocrit level of 42 3% compared to those targeted to 30 3% (202). It has also been reported... 

Colditz GA, Tuden RL, Oster G. Rates of venous thrombosis after general surgery combined results of ranomised clinical trials. Lancet 1986 2(8499) 143-146. 

Recently, several reports comparing the effects of heparin and hirudin on various parameters have become available. A study comparing heparin and recombinant hirudin for the prophylaxis of deep venous thrombosis (DVT) provided impressive data in favor of hirudin. In a second study, LMWHs also were compared with hirudin for postsurgical prophylaxis of DVT the results favored hirudin. Both studies emphasize an important point about the validity of well-designed clinical trials, It is important to understand that the efficacy and safety of a new drug may not be determined by trials for a single indication, Therefore, clinical trials are needed for various specific indications. 

DOXORUBICIN THALIDOMIDE t risk (up to sixfold) of deep venous thrombosis in patients with multiple myeloma compared with those treated without doxorubicin Uncertain. Attributed to doxorubicin contributing to the thrombogenic activity Avoid co-administration - except in clinical trials... 

Dermatan sulfete and heparan sulfitte have provided disappointing results to date. The synthetic heparin pentasaccharide, which acts strictly via die inhibition of fector Xa, has been successfidly used in angioplasty and is presently imdergoing clinical trial for the prophylaxis of venous thrombosis in orthope c surgical patients. Various large scale clinicd trials have been organized. In addition, several derivatives of oligosaccharides are also developed with multiple protease inhibitory action. 

In 14 clinical trials of prothrombin complex concentrates for reversal of oral anticoagulation therapy, seven of 460 patients (1.5%) had thrombotic events, three thrombotic strokes, two cases of deep venous thrombosis, and two non-Q-wave myocardial infarctions [31 ]. However, in 40 patients taking oral anticoagulants, who needed cardiopulmonary bypass surgery, and of whom 20 were treated with prothrombin complex concentrates, no thrombotic events occurred [35 ]. 

A number of rather limited trials have been reported with agents such as aspirin, dipyridamole, sulfinpyrazone and cyproheptadine in a variety of clinical conditions. An example is a rather dramatic effect seen with aspirin and dipyridamole in a case of thrombotic thrombocytopenic purpura.39 variable results with these agents have also been previously reported in transient cerebral ischemia,40,41 platelet consumption following prosthetic heart valve surgery,42,43 and postsurgical venous thrombosis.44 Certainly results from clinical studies of a larger scale, such as those currently underway in the United States and Canada, will have to be completed before a valid assessment of the potential clinical utility of these agents can be made.45,46... 

---