Skip to content

Final Results of RE-VERSE AD Study

  • by

Dr. Charles Pollack discusses the Final Results of RE-VERSE AD Study at The International Society onThrombosis and Haemostasis Meeting in Berlin, July, 2017

I’m charlie pollock from thomas jefferson university in philadelphia pennsylvania and i’m pleased to share with you top-line results from the final chord analysis of the reverse ad study a study of a dairy scissor map a specific reversal agent for dabigatran in patients with either emergency bleeding complications or surgical complications requiring reversal prior

To the procedure reverse ad was a multicenter prospective open label single-arm phase three study they were conducted in 173 sites in 39 countries over about two and a half years and we looked at patients who were being treated with the bigoted rennet exa late over 90% of them were under big a trend for stroke prevention atrial fibrillation who required reversal

For one of two reasons they were called group a if they presented on the bigger trend with uncontrolled or life-threatening bleeding and they were called group b if they presented on the bigger trend not bleeding but with a need for an emergency sharp procedure of some sort whether scalpel or catheter based these patients were assessed for inclusion in the study

Based only on clinical criteria there was no laboratory value or vital sign requirement to document the patient’s eligibility this was a decision made entirely by the treating clinician and whether patients were in group a or group b they all got five grams of the darius’s amount as has given us to two and a half gram bolus 5 grams of the dose that should reverse

The 99% column dabigatran levels seen in the large real life study of the bigger trend versus vitamin k antagonist atrial fibrillation a few years back the primary end point of the study again independent of group assignment was the maximum reversal of the anticoagulant effects of the bigger trend as measured by either dilute thrombin tom or eccrine clotting time

Both of which correlated in linear fashion to dabigatran concentrations across a broad range within four hours and you see on the slide here that there are multiple time intervals at which this was assessed we continue following patients out to 90 days with important secondary endpoints including time to cessation of bleeding in patients who didn’t have a trineo

Hemorrhage from the group a cohort and in the group d cohort the time to surgery and the hemostasis before during and after the procedure as determined by the treating clinician secondary and points of interest included thrombotic events after reversal when anticoagulation or other any thrombotic therapy which restarted overall mortality the impact of i darius ism

Ab on the bigger trend anticoagulation is assessed by the activated partial thromboplastin time and the thrombin time both of which are of course more readily available around the world than btt and ect drug levels of both the bigotry and racism at and we look to the development of anti-drug antibodies to add aces a map out to ninety days the primary results of

The study were quite straightforward the median maximum reversal within four hours as measured by the two clotting analyses was 100% and the confidence intervals as you see were as tight as they could be we did receive similar results when we looked at both the apt t and the tt in the central laboratory now results of course may vary a bit in local laboratories

Because they’re different reagents that are used for these studies in different hospitals and importantly the dilute drummond time normalized within four hours in 99% of group a patients the bleeders and almost the same 99 percent in group b patients to pre procedural patients so a striking endpoint that was hit all the way here’s a graphic representation of that

Looking at dtt in group a on the left and group b on the right just to walk you through how these data are presented this is a box and whiskers plot you have the dtt on the y-axis the tongue on the x-axis the boxes represent the 25th to 75th percentile of the value in this case dtt the line in the middle represents the median the whiskers above and below the box

Represent the 10th and 90th percentile and the dots above them below those represent the 95th and 5th percentile the two blue arrows represent the time of administration of the two different vials of the day racism ever remember all these patients got five grams and the shaded area represents the the upper limit of normal of the dilute momentum so what you see

Is an immediate reduction in the dtt to below the limit of coagulation even between the two vials of a day system at but certainly out after full dosing and persisting out to 24 hours in almost all patients so a very consistent effect that is is predictable and durable on this slide on the left-hand side we see groups a and b together looking at unbounded bigoted

Ran so you see here that the results you saw in the previous slide do in fact correlate to the actual concentrations of d’vega trend and again because the aptt is more readily available in hospital than our ect or dtt we show here central lab a ptt where the effects of a de souza map are shown just as clearly as they are on the other studies interesting secondary

Endpoints from group a and group b here in group a we look at bleeding cessation as recorded locally within 24 hours now unfortunately not all of these patients were accessible for example we couldn’t look at a cranial hemorrhage to bleeding because we didn’t mandate serial ct scans for non-hodgkins 120 of those where jia bleeds 78 were non gi na nice eh and of

Those accessible patients the median time to locally reported bleeding cessation was two and a half hours so remembering that day racism have is not a hemostatic agent it’s a reversal agent this means that the providers after reversal did a good job of stabilizing these patients and would get a nice tight interval there until bleeding cessation was reported in group

B the pre procedural patients we looked at perry procedural stasis and it’s important to note that the time from administration of a de souza magic procedure was only one point six hours and we asked the local investigators to classify hemostasis as they saw it based on a scale of normal as if there were no any coagulation at all or abnormal divided an amount

Moderate and severe and you see the definitions of those in the box on the right but the important message here is that even less than two hours at reversal in excess of 93 percent of patients had normal hemostasis of the rest there was either mild or moderately abnormal hemostasis and none were classed as severely abnormal so in conclusion reverse ad showed us

That in a cohort of elderly multi morbid patients taking the bigger trend who presented with life-threatening emergencies a standard dose of 5 grams of a darius’s amad resulted in immediate complete and sustained reversal of the bigger trainee coagulation we saw prompt cessation of extracranial bleeding in the group a patience and good hemostasis at the time of

Procedure in the group b patients not discussed in the summary but promptly initiation of antithrombotic therapy was allowed on the protocol after reversal and it was done in safe fashion with no thrombotic effect and consistent with both preclinical data and the interim analysis of reverse ad we saw no safety concerns associated with this drug and i’m happy to

Report that at the time of presentation of the data at the international society of thrombosis of hemostasis in berlin we had simultaneous publication of the full cohort analysis in new england journal of medicine

Transcribed from video
Final Results of RE-VERSE AD Study By Thrombosis.TV