Idarucizumab – Praxbind – Reverses Anticoagulant Effect of Pradaxa Prior To Emergency Surgery

MedicalResearch.com Interview with:

Thomas Seck, M.D., vice president Clinical Development and Medical Affairs, Primary Care Boehringer Ingelheim Pharmaceuticals, Inc.

Dr. Thomas Seck

Thomas Seck, M.D., vice president
Clinical Development and Medical Affairs
Primary Care
Boehringer Ingelheim Pharmaceuticals, Inc.

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

Response: This is a new subanalysis of the phase III RE-VERSE AD™ study, which evaluated the safety and efficacy of idarucizumab, marketed in the U.S. as Praxbind®, in reversing the anticoagulant effect of Pradaxa® (dabigatran etexilate mesylate). This data assessed idarucizumab in a subset of patients requiring an urgent procedure or emergency surgery.

The analysis found that idarucizumab rapidly and completely reversed the anticoagulant effect of dabigatran in approximately 98 percent of patients based on dTT. The median time between administration of idarucizumab and start of surgery was 1.7 hours for patients requiring abdominal procedures, 1.9 hours for orthopedic procedures, 1.4 hours for vascular procedures, 1.3 hours for drainage procedures and 1.2 hours for catheter procedures. Among these patients, periprocedural homeostasis was assessed as normal in more than 92 percent of patients, across all surgery types.

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Oral Semaglutide As Effective As Injectable In Reducing A1C and Weight Loss

MedicalResearch.com Interview with:

Melanie J Davies CBE MB ChB MD FRCP FRCGP Professor of Diabetes Medicine  NIHR Senior Investigator Emeritus Diabetes Research Centre Leicester Diabetes Centre – Bloom University of Leicester

Prof. Davies

Melanie J Davies CBE MB ChB MD FRCP FRCGP
Professor of Diabetes Medicine
NIHR Senior Investigator Emeritus
Diabetes Research Centre
Leicester Diabetes Centre – Bloom
University of Leicester

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

Response:  This was the first study to test the effectiveness of an oral GLP-1 in patients with type 2 diabetes.

The main findings were that compared to both placebo and a GLP-1, Semaglutide, delivered by sub-cutaneous injection weekly, the oral therapy delivered once a day produced better results than placebo and similar results to injectable GLP-1 with regard to reductions in HbA1c and weight loss.

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Standard or Low Dose Alteplase in Acute Ischemic Stroke–Does It Matter?

MedicalResearch.com Interview with:

Craig Anderson | MD PhD FRACP Executive Director  Professor of Neurology and Epidemiology, Faculty of Medicine, UNSW Sydney Neurologist, Neurology Department, Royal Prince Alfred Hospital The George Institute for Global Health at Peking University Health Science Center Haidian District | Beijing, 100088 P.R. China

Prof. Anderson

Craig Anderson | MD PhD FRACP
Executive Director
Professor of Neurology and Epidemiology, Faculty of Medicine, UNSW Sydney
Neurologist, Neurology Department, Royal Prince Alfred Hospital
The George Institute for Global Health at Peking University Health Science Center
Haidian District | Beijing, 100088 P.R. China

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

Response:  There is much controversy over the benefits of a lower dose of intravenous alteplase, particularly in Asia, after the Japanese regulatory authorities approved a dose of 0.6 mg/kg 10 years ago compared to the US FDA and other regulatory authorities approving 0.9 mg/kg 20 years ago.  The investigator inititiated and conducted ENCHANTED trial aimed to determine the effectiveness and safety of these two doses in an international multicentre pragmatic open design.

The main results did not confirm the low-dose to be statistically ‘non-inferior’ partly due to the primary outcome measure chosen and partly due to the statistical approach, but it did confirm that the lower dose was safer with less risk of the major complication of this treatment, that of major bleeding in the brain.  However, it would appear that this safety effect was offset by some reduce efficacy in terms of functional recovery.

The aim of this secondary analysis of the trial data was to examine in more detail the differences between low and standard dose alteplase according to the participants’ age, ethnicity (Asian vs non-Asian) and severity of neurological deficit at the time of treatment.  We did this because the popular belief is that a lower dose might be preferred in older people, and Asians, because of the potential for more likelihood of bleeding, and preferentially to use the standard dose in those with more severe strokes potentially due to greater ‘clot burden’ from a blocked artery to the brain.

The results showed that the main findings on the outcome of surviving free of disability were the same according to age, ethnicity and stroke severity – that is, there was no preferential dose in any of these groups.  Similarly, the safety benefit of low dose alteplase on brain haemorrhage, did not clearly translate into clinical disability outcomes in any of the patient groups studied.

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IPF: Combination of Nintedanib and Pirfenidone May Have Added Benefit With Manageable Side Effects

MedicalResearch.com Interview with:

Professor Carlo Vancheri Professor of Respiratory Medicine, University of Catania, Italy and Director of the Regional Referral Centre for Rare Lung Diseases and the Laboratory of Experimental Respiratory Medicine.

Prof. Vancheri

Professor Carlo Vancheri
Professor of Respiratory Medicine,
University of Catania, Italy and Director of the Regional Referral Centre for Rare Lung Diseases and the Laboratory of Experimental Respiratory Medicine.

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

Response: The aim of Boehringer Ingelheim’s INJOURNEY trial was to investigate the safety profile of Ofev (nintedanib) in combination with pirfenidone in treating patients with idiopathic pulmonary fibrosis (IPF). Nintedanib and pirfenidone, the only two FDA-approved drugs for the treatment of IPF, are able to slow down the progression of the disease, reducing the forced vital capacity (FVC) decline of about 50%, but this is not a cure. The target for the future is to have even more effective treatments. In the meanwhile, it is necessary to optimize the use of the available drugs. The medical treatment of other pulmonary diseases such as COPD, asthma or pulmonary hypertension is already based on different combinations of drugs.

This 12-week, open-label, randomized study was designed to evaluate the safety, tolerability and pharmacokinetics of nintedanib with add-on pirfenidone, compared with nintedanib alone in patients with IPF. Change in FVC, the established efficacy endpoint in IPF trials, was evaluated as an exploratory endpoint.

The primary endpoint of the INJOURNEY trial was the percentage of patients with on-treatment gastrointestinal adverse events from baseline to week 12 of randomized treatment, and the results showed that the combination of nintedanib and add-on pirfenidone resulted in a manageable safety and tolerability profile, similar to the profile of each drug individually in the majority of patients. Results also indicated there may be a slower decline in FVC in patients treated with pirfenidone along with nintedanib compared with nintedanib alone, suggesting a potential benefit of the combination. However, further research will be necessary to fully evaluate the efficacy of the combination.

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Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation 

MedicalResearch.com Interview with:

Professor Christopher P. Cannon MD Executive Director, Cardiometabolic Trials, Baim Institute Cardiologist Brigham and Women's Hospital Baim Institute for Clinical Research Columbia University College of Physicians and Surgeons

Dr. Cannon

Professor Christopher P. Cannon MD
Executive Director, Cardiometabolic Trials, Baim Institute
Cardiologist Brigham and Women’s Hospital
Baim Institute for Clinical Research
Columbia University College of Physicians and Surgeons

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

Response: The trial explored whether a dual therapy approach of anticoagulation and P2Y12 antagonist – without aspirin – in non-valvular atrial fibrillation (AF) patients following percutaneous coronary intervention (PCI) and stent placement would be as safe, and still efficacious, as the current standard treatment – triple therapy. For more detailed background on the study, readers may want to review the first paragraph of the article in the New England Journal of Medicine.

Results showed significantly lower rates of major or clinically relevant non-major bleeding events for dual therapy with dabigatran, when compared to triple therapy with warfarin.

In the study, the risk for the primary safety endpoint (time to major or clinically relevant non-major bleeding event) was 48 percent lower for dabigatran 110 mg dual therapy and 28 percent lower for dabigatran 150 mg dual therapy (relative difference), with similar rates of overall thromboembolic events.

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COMPASS Study Finds Rivaroxaban -XARELTO® – Plus Aspirin Reduces Adverse Events in Patients With Heart Disease or PAD

MedicalResearch.com Interview with:

John Eikelboom MBBS Associate Professor, Division of Hematology & Thromboembolism Department of Medicine Canada Research Chair in Cardiovascular Medicine Canadian Institutes for Health Research McMaster University

Dr. Eikelboom

John Eikelboom MBBS
Associate Professor, Division of Hematology & Thromboembolism
Department of Medicine
Canada Research Chair in Cardiovascular Medicine
Canadian Institutes for Health Research
McMaster University

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

Response: Cardiovascular disease affects 1 in 25 persons around the world and a total of more than 300 million individuals. Thrombus formation at the site of a ruptured atherosclerotic plaque is the commonest mechanism of myocardial infarction and ischemic stroke in patients with cardiovascular disease. Aspirin is effective for the prevention of these complications but reduces the risk by only 19% during long term therapy.

Rivaroxaban has previously been tested in the ATLAS ACS-2 TIMI 51 trial at doses of 2.5 mg twice daily or 5 mg twice daily on top of background antiplatelet therapy and has been shown to reduce major adverse cardiovascular events as well as mortality. We tested these same doses of rivaroxaban for the prevention of cardiovascular death, stroke or myocardial infarction in patients with stable cardiovascular disease.

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Does Spironolactone Work In Acute Heart Failure?

MedicalResearch.com Interview with:

Javed Butler, MD, PhD Chief of the Cardiology Division Dr. Vincent Yang, Simons Chair in Internal Medicine Stony Brook University

Dr. Butler

Javed Butler, MD, PhD
Chief of the Cardiology Division
Dr. Vincent Yang, Simons Chair in Internal Medicine
Stony Brook University

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

Response: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF. We therefore studies high dose spironolactone in patients with AHF. Unfortunately all of our primary and secondary endpoints were not different between spironolactone and placebo arms.

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Phase III Study of Stivarga (Regorafenib) For Progressed Hepatocellular Carcinoma

MedicalResearch.com Interview with:

Dr. Jordi Bruix, MD Professor of Medicine University of Barcelona Director of the Barcelona Clinic Liver Cancer (BCLC) Group Liver Unit Hospital Clinic of Barcelona

Dr. Bruix

Dr. Jordi Bruix, MD
Professor of Medicine
University of Barcelona
Director of the Barcelona Clinic Liver Cancer (BCLC) Group Liver Unit
Hospital Clinic of Barcelona

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

Response: The RESORCE Phase III pivotal trial is an international, multicenter, placebo-controlled trial which investigated the efficacy of Stivarga (regorafenib) in adults with Child-Pugh A and Barcelona Clinic Liver Cancer Stage Category B or C hepatocellular carcinoma (HCC) who had documented disease progression following first-line treatment with Nexavar (sorafenib).

Trial participants were administered a daily oral 160mg dose (three weeks on/ one week off) of regorafenib plus best supportive care (BSC), or placebo plus BSC.

Results from the trial demonstrated that participants treated with regorafenib experienced a statistically significant and clinically meaningful improvement in the study’s primary endpoint—overall survival (OS). Participants treated with regorafenib demonstrated a median overall survival of 10.6 months vs. 7.8 months with placebo.

At ASCO 2017, an exploratory analysis evaluated the impact of baseline alpha-fetoprotein (AFP) and c-Met as predictors of poor prognosis in patients enrolled in the RESORCE trial (Abstract #4078).

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PCSK9 Inhibitor Praluent Added to Statins Improved Lipid Profile in Diabetes

MedicalResearch.com Interview with:

Dr-Robert-R-Henry.jpg

Dr. Henry

Robert R. Henry, M.D.
Professor of Medicine
Member of the ODYSSEY DM Steering Committee and
Director of the Center for Metabolic Research
VA San Diego Healthcare System

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

Response: The ODYSSEY DM-DYSLIPIDEMIA trial was a randomized, open-label, parallel-group study designed to evaluate the superiority of Praluent versus usual care in 413 patients with type 2 diabetes with mixed dyslipidemia at high cardiovascular (CV) risk, not adequately controlled with maximally tolerated dose (MTD) statins. The primary endpoint was percent change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to week 24.

In ODYSSEY DM-DYSLIPIDEMIA, Praluent 75 mg was added to MTD statins, with dose adjusted at week 12 to 150 mg every two weeks if their non-HDL-C was greater than or equal to 100 mg/dL at week 8. Approximately 64 percent of patients reached their lipid goals with the Praluent 75 mg dose.

Results from the ODYSSEY DM-DYSLIPIDEMIA study found that Praluent added to MTD statins showed significant reduction in non-HDL-C and other lipid parameters compared to those on usual care.

Praluent was superior to usual care in lowering non-HDL-C (37.3 percent and 4.7 percent, for the usual care arm). The mean difference between the two treatment arms was -32.5 percent (p<0.0001).

Praluent in combination with MTD statins reduced LDL-C by 43 percent from baseline compared to a 0.3 percent increase for usual care (p<0.0001). Treatment with Praluent also improved the overall lipid profile.

There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Furthermore, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk.

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Adding Praluent (Alirocumab) To Statins Reduces LDL in High Cardiovascular Risk Diabetics

MedicalResearch.com Interview with:

Lawrence Leiter, M.D. MDCM, FRCPC, FACP, FACE, FAHA Chair of the ODYSSEY DM Steering Committee and Director of the Lipid Clinic at the Li Ka Shing Knowledge Institute St. Michael’s Hospital University of Toronto, Canada

Dr. Lawrence Leiter

Lawrence Leiter, M.D. MDCM, FRCPC, FACP FACE, FAHA
Chair of the ODYSSEY DM Steering Committee and
Director of the Lipid Clinic at the Li Ka Shing Knowledge Institute
St. Michael’s Hospital
University of Toronto, Canada

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

Response: The ODYSSEY DM-INSULIN trial was a randomized, double-blind, placebo-controlled, multicenter study that evaluated alirocumab (Praluent) in 517 patients with insulin treated type 1 and type 2 diabetes with high cardiovascular (CV) risk and hypercholesterolemia despite maximally tolerated dose (MTD) statins. The primary endpoint was percent change in calculated LDL-C from baseline to week 24.

Alirocumab 75 mg every two weeks was added to MTD statins, with the dose increased at week 12 to 150 mg every two weeks if the LDL-C at week 8 was greater than or equal to 70 mg/dL. In fact, only about 20% of the alirocumab treated participants required the higher dose.

Results of the type 2 diabetes study population (n=441) showed that the addition of alirocumab to MTD statin therapy, reduced LDL-C by 48.2 percent from baseline compared to a 0.8 percent increase for placebo. The mean difference between the two treatment arms was -49 percent (p<0.0001). Treatment with alirocumab also improved the overall lipid profile. Furthermore, no new safety issues were identified.

There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Additionally, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk.

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