Clinical trials bleeding

Table 2.11. CLINICAL TRIALS BLEEDING RISK AND SAFETY ...

Celecoxib, which has a low selectivity for COX-2 compared to COX-1, is still available, although its more selective successor, valdecoxib has been withdrawn. Etoricoxib, the successor to rofecoxib, is marketed in Europe but not in the USA. In a large multinational clinical trial, etoricoxib caused no more thromboembolic events than diclofenac, but after 18 months the incidence of gastrointestinal ulcers and bleeding was the same for both drugs [4]. 

While bleeding is the most frequently observed symptom of DIC, thrombotic events cause most of the mortality. Heparin is an effective anticoagulant with the potential to inhibit thrombin formation and function however, its use is limited by the potential for bleeding. Clinical trials of heparin in DIC have not shown a consistent benefit. DIC patients most likely to benefit... 

The product displays a mean serum half-life of 18.8 h in humans. It has been evaluated in four clinical trials involving a total of 128 subjects and in the context of both spontaneous bleeding and surgery. Some 88 per cent of the total infusions administered for bleeding were rated as providing a good or excellent response. Reported side effects, although uncommon, included hypersensitivity, as well as headache, fever and nausea. BeneFix is marketed by Wyeth. 

Hematological agents In clinical trials in patients undergoing PTCA/PCI, coadministration of bivalirudin with heparin, warfarin, thrombolytics, or GPIIb/llla inhibitors was associated with increased risks of major bleeding events compared with patients not receiving these concomitant medications. There is no experience with coadministration of bivalirudin and plasma expanders such as dextran. 

Adverse Events Other Than Bleeding Occurring in 5% of Patients in Either Treatment Group in Randomized Clinical Trials ... 

HIV-infected women Although megestrol has been used extensively in women for endometrial and breast cancers, its use in HIV-infected women has been limited. All the women in the clinical trials reported breakthrough bleeding. 

Celecoxib (Celebrex) and rofecoxib (Vioxx) are highly selective COX-2 inhibitors. Because of this, they produce less erosion of the GI mucosa and cause less inhibition of platelet aggregation than do the nonselective COX inhibitors. Short-term (6 months-to a year) clinical trials have shown that celecoxib and rofecoxib produce less GI toxicity than nonselective NSAIDs. However, serious GI bleeding and ulceration have occurred in patients taking these drugs, and long-term prospective studies of their safety have yet to be completed. Like the nonselective NSAIDs, the selective COX-2 inhibitors can produce renal side effects such as hypertension and edema. 

Recombinant t-PA has also been approved for use in acute ischemic stroke within 3 hours of symptom onset. In patients without hemorrhagic infarct or other contraindications, this therapy has been demonstrated to provide better outcomes in several randomized clinical trials. The recommended dose is 0.9 mg/kg, not to exceed 90 mg, with 10% given as a bolus and the remainder during a 1 hour infusion. Streptokinase has been associated with increased bleeding risk in acute ischemic stroke when given at a dose of 1.5 million units, and its use is not recommended in this setting. 

Clinical trials of desogestrel implants showed that they were effective, but with bleeding irregularities and ovarian cysts as the primary adverse effects (4). 

Affandi B. An integrated analysis of vaginal bleeding patterns in clinical trials of Implanon. Contraception 1998 58(Suppl 6) S99-S107. 

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