Stroke: Experimental Antiplatelet Antibody Only Attacks Clots, Without Increasing Bleeding Risk

MedicalResearch.com Interview with:

MedicalResearch.com Interview with:Martine Jandrot-Perrus MD, PhD.Emeritus Research ProfessorInserm University Paris DiderotActicor BiotechHôpital BichatFrance

Dr. Jandrot-Perrus


Martine Jandrot-Perrus MD, PhD.
Emeritus Research Professor
Inserm University Paris Diderot
Acticor Biotech
Hôpital Bichat
France 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Blood platelets are key actors in thrombosis a leading cause of global mortality estimated to account for 1 in 4 death worldwide in 2010.

Thrombosis is associated with cardiovascular diseases (myocardial infarction, stroke, lower limb ischemia, venous thromboembolism), and with numerous pathologies such as cancer, infections or inflammatory diseases. Currently available antiplatelet drugs are the cornerstone of therapy for patients with acute coronary syndromes. However, these drugs all carry an inherent risk of bleeding that restricts their use in sensitive populations and when arterial thrombosis occurs in the cerebral territory. At present the only acute treatment option available for ischemic stroke consists in revascularization by thrombolysis, and/or mechanical thrombectomy. But the number of patients eligible to these treatments is low (» 15% of all patients) and the success rate does not exceed 50%. The responsibility of platelets in the failure for thrombolysis / thrombectomy to restore vascular patency is strongly suspected.

There is thus a clear medical need for new antiplatelet drugs with an improved safety profile. We set out to develop ACT017, a novel, first in class, therapeutic antibody to platelet glycoprotein VI with potent and selective antiplatelet effects. The interest of GPVI resides in the fact that it’s a receptor involved in the development of occlusive thrombi but that it is not strictly required for physiological hemostasis.
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Clot-Busting Catheter Procedure for DVT May Reduce Symptoms In Some Patients

MedicalResearch.com Interview with:
Suresh Vedantham, M.D
.
Principal Investigator, ATTRACT Trial
Professor of Radiology & Surgery
Mallinckrodt Institute of Radiology
Washington University School of Medicine 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:   About 300,000 Americans each year are diagnosed with a blood clot (deep vein thrombosis, DVT) for the first time.  In total, about 600,000 Americans have a DVT each year, as noted in the 2008 Surgeon General’s Call to Action.

Despite the use of standard treatment (blood thinning drugs and compression stockings), about 40% of DVT patients develop a long-term complication called post-thrombotic syndrome (PTS).  PTS impairs patients’ quality of life and typically causes chronic pain and swelling of the leg that occur on a daily basis. In many patients, this leads to major disability the prevents them from walking, working, or conducting normal daily activities. Some patients develop painful open sores on the leg called “venous ulcers”, that are difficult to heal.

Pharmacomechanical catheter-directed thrombolysis (“PCDT”) is a minimally-invasive treatment that removes blood clots through a tiny (2-3 mm) incision using the clot-busting drug tissue plasminogen activator (TPA) along with catheter-based devices that can chew up the clots. The benefits and risks of PCDT have not before been evaluated for DVT treatment in a rigorous study.

     The final results of the ATTRACT Trial, which was primarily sponsored by the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH), are being published in The New England Journal of Medicine.  ATTRACT, the most rigorous study to date of clot-busting treatment for DVT, was a multicenter randomized controlled trial comparing PCDT and standard therapy versus standard therapy alone in 692 patients with above-knee DVT. This landmark study, conducted in 56 U.S. hospitals, was led by Principal Investigator Dr. Suresh Vedantham, Professor of Radiology & Surgery at the Mallinckrodt Institute of Radiology at Washington University in St. Louis, along with outstanding DVT researchers at McMaster University (Hamilton, Ontario [Canada]), the Massachusetts General Hospital (Boston, MA), and the Mid America Heart Institute (Kansas City, MO).  

The primary study result is that for most patients with DVT, the addition of PCDT to standard therapy does not prevent the development of PTS.  Because the use of PCDT involves a small but significant increase in major bleeding complications, it should not be routinely used as first-line DVT treatment.  However, PCDT did reduce the severity of PTS and appeared likely to provide better relief of DVT-related leg pain and swelling.  Further analyses will determine which DVT patients are most likely to experience these benefits.

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Idarucizumab For Dabigatran Reversal: Updated Results Of The Re-verse Ad Study

MedicalResearch.com Interview with:

Dr. Charles Pollack MD Professor of Emergency Medicine Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia.

Dr. Charles Pollack

Dr. Charles Pollack MD
Professor of Emergency Medicine
Sidney Kimmel Medical College at
Thomas Jefferson University, Philadelphia.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: RE-VERSE AD™ is a multinational, open-label cohort Phase III trial studying the safety and efficacy of idarucizumab (PRAXBIND) to reverse the anticoagulant effects of dabigatran (PRADAXA) in patients with life-threatening or uncontrolled bleeding, or those who require emergency procedures.

It is the largest patient study investigating a reversal agent for a novel oral anticoagulant (NOAC) in real world emergency settings. At the American Heart Association’s Scientific Sessions 2016, we presented updated results from 494 patients participating in the ongoing study, showing that administration of 5g of idarucizumab immediately reversed the anticoagulant effect of dabigatran.

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