Study of dabigatran in mechanical heart valve patients halted

[Lynlw]

The trials weren't in the US, but Canada and several European countries. I know this was one of the drugs some were hoping would be approved to replace Coumadin for valves, so it's a shame it doesnt look like it will any time soon.

http://www.theheart.org/article/1487131.do
"Boehringer Ingelheim is halting the RE-ALIGN trial investigating the use of dabigatran (Pradaxa) in patients with artificial heart valves [1]. The phase 2 dose-ranging study was stopped because investigations into the dosing regimen "did not achieve the desired results," according to the company.

The study was testing three doses of dabigatran in patients with newly or previously implanted mechanical aortic valves, but concerns have been raised about the risk of valve thrombosis with the newer anticoagulant. In September 2012, as reported by heartwire, Canadian physicians reported the cases of two women who had undergone valve replacement years prior and had been faring well on warfarin but who subsequently suffered valve thrombosis when they were switched to dabigatran.

Dabigatran is not approved for patients with mechanical valves. It is approved by the Food and Drug Administration for preventing strokes and systemic embolism in patients with nonvalvular atrial fibrillation as well as in preventing venous thromboembolism following elective knee- or hip-replacement surgery.

"The presence of an artificial heart valve in patients is a clinical condition that is distinct from those for which dabigatran is an approved treatment," Boehringer Ingelheim stated in a press release. "In view of the interim trial results, the company is currently in discussions with the relevant regulatory authorities to reinforce the product label text accordingly and to discuss appropriate communication to physicians and relevant healthcare providers."

The RE-ALIGN study was started in December 2011, and approximately 370 patients were expected to be enrolled. The study's completion date was initially sometime in 2018"

Here is a link with info about the trial and where it was taking place http://clinicaltrials.gov/ct2/show/study/NCT01505881?term=REALIGN&rank=1&show_locs=Y#locn

 

[pellicle]

seems a chicken vs egg problem to me (unless I'm misreading this).

They are wanting to test if it can be used but can't test because its not approved?

 

[ski girl]

My interpretation is that they halted the trial because the drug wasn't working and they didn't want to (actually, aren't allowed to) continue the trial when there is evidence of poor patient outcomes. I.e. the two women cited who were fine on warfarin but had thrombosis on the new drug . . . .

 

[Lynlw]

seems a chicken vs egg problem to me (unless I'm misreading this).

They are wanting to test if it can be used but can't test because its not approved?

No Ski has it right, they started the trials and stopped them because the results weren't good. (JUST MY guess but, most likely werent as good as Coumadin with normal INRs. Kind of like the asperin trials ON-X stopped in germany that were stopped for clots/death a few years ago)

I dont think the 2 women in Canada were part of the trial , I believe in that case the doctors just wrote for it off label, but it is confusing they mentioned it in this article.

FWIW things usually arent approved before the trials, altho in some cases it is approved for one group, but trying to get approval for another group of patients, thats why you have t sign all kinds of forms to agree to be part of the trials

 

[pellicle]

hi

ok, I was confused by:

"The presence of an artificial heart valve in patients is a clinical condition that is distinct from those for which dabigatran is an approved treatment," Boehringer Ingelheim stated in a press release. "In view of the interim trial results, the company is currently in discussions with the relevant regulatory authorities to reinforce the product label text accordingly and to discuss appropriate communication to physicians and relevant healthcare providers."

when the substance was this:

In September 2012, as reported by heartwire, Canadian physicians reported the cases of two women who had undergone valve replacement years prior and had been faring well on warfarin but who subsequently suffered valve thrombosis when they were switched to dabigatran.

thanks

 

[pellicle]

PS

would like to know how they determined:

subsequently suffered valve thrombosis

like did they have a stroke?

 

[Lynlw]

PS

would like to know how they determined:


like did they have a stroke?

That would be my guess, or a clot in the valve etc. Just like they do in all the studies for Valve choice or articles on long term use of certain valves or INR ranges. Of course there can be small clots that don't do any damage so they wouldnt look for clots, just count ones they know about.

I'm not quite sure what you are asking in the previos post, but by this

"The presence of an artificial heart valve in patients is a clinical condition that is distinct from those for which dabigatran is an approved treatment," Boehringer Ingelheim stated in a press release. "In view of the interim trial results, the company is currently in discussions with the relevant regulatory authorities to reinforce the product label text accordingly and to discuss appropriate communication to physicians and relevant healthcare providers"

Pretty much they are saying in Pradaxa is NOT reccomended for valve patients, (it is approved for Afib, some short term post op orthopedic cases etc) and they want to work on making sure US doctors know don't use it off label for Valve patients. Even tho the US hospitals didn't take part in the RE-ALIGN trials, because of the results they want to make a statement, maybe change warning on lable ect.

 

[pellicle]

Hi

That would be my guess, or a clot in the valve etc. Just like they do in all the studies for Valve choice or articles on long term use of certain valves or INR ranges. Of course there can be small clots that don't do any damage so they wouldnt look for clots, just count ones they know about.

makes me wonder how they can do that ...

I'm not quite sure what you are asking in the previos post, but by this

"The presence of an artificial heart valve in patients is a clinical condition that is distinct from those for which dabigatran is

Oh, I was just trying to explain what I'd read that was why I got the wrong idea ... which you guys have set me straight on

 

[pellicle]

makes me wonder how they can do that ...

perhaps this?
http://en.wikipedia.org/wiki/D-dimer

 

[ElectLive]

Thanks Lyn. You know, one arm of the dosing study was actually halted back in October before this official end now to the study as a whole. There were two arms initially - one beginning immediately after valve replacement and another at least 3 months post op. The arm halted in October was the first one, no surprise there. I'm actually astonished Boehringer Ingelheim even had that arm at this stage (no evidence yet, in other words, only the very initial dosing study) given the increased stroke risk in the first 3 months with any valve replacement. Take On-X and Proact for instance, that protocol - now trialed and under FDA review - does not begin until 3 months post op, and it is much much further along from a patient year experience perspective.

There's some additional info on all of this in this October article (http://www.forbes.com/sites/larryhusten/2012/10/23/setback-for-trial-studying-dabigatran-after-mechanical-valve-surgery/) that sheds a little light on what's actually been happening so far. Here's also the official press release from the manufacturer: http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2012/11_december_2012dabigatranetexilate1.html. One interesting thing to me is that the adverse events so far appear (very limited info, though) to be primarily stroke related. I was suspecting that bleeding events could end up being just as likely since one of the doses being used for the valve patients had been used in the A-fib trial and was not approved, since it was inferior to Warfarin (higher amounts of bleeding with no net benefit in stroke reduction). I mentioned this is another post with a little more detail here: http://www.valvereplacement.org/forums/showthread.php?39453-Blood-thinners-for-life&p=511332&highlight=#post511332.

 

[coffeelover]

Interesting thread. Thanks for sharing the info.

 

[ElectLive]

The FDA issued a safety advisory yesterday...turns out Pradaxa (dabigatran) was showing inferiority to Warfarin in both respects (bleeding and clotting): http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm332949.htm.

Excerpt from the same:

"A clinical trial in Europe (the RE-ALIGN trial) was recently stopped because Pradaxa users were more likely to experience strokes, heart attacks, and blood clots forming on the mechanical heart valves than were users of the anticoagulant warfarin. There was also more bleeding after valve surgery in the Pradaxa users than in the warfarin users."

 

[dick0236]

Excerpt from the same:

"A clinical trial in Europe (the RE-ALIGN trial) was recently stopped because Pradaxa users were more likely to experience strokes, heart attacks, and blood clots forming on the mechanical heart valves than were users of the anticoagulant warfarin. There was also more bleeding after valve surgery in the Pradaxa users than in the warfarin users."

After 45+ years, event free* on warfarin, I think I'll stay with what I know and trust.

*stroke in 1974 that was my fault, not the drugs fault.

 

[Protimenow]

I'm with Dick. I'm only 21 years post-op. But a medication that costs about a dime a day, whose effects can be easily tested (blood draws or meter tests), and whose effects can be fairly easily controlled (and reversed, if necessary), sounds like a pretty solid alternative to a new drug that costs about $8 a day, has no apparent antidote, and still probably requires occasional testing for efficacy.

If some magic bullet comes along that prevents embolism at the valve, costs a few cents a day (or, perhaps, can work in a once monthly dose), can be reversed if necessary, and doesn't require monitoring, I'd be interested in trying it - but I don't think we'll be seeing this drug for some time (if ever).

For now, I'm comfortable with warfarin.

 

[ElectLive]

Even more info from the FDA, including the all important data: http://www.fda.gov/Drugs/DrugSafety/ucm332912.htm

Early numbers, with inherent limitations, and no real analysis, but wow, all the same. There certainly doesn't seem to be any magic pill to be found here.