Clinical Trials – New Horizons
~ Pharmacology News ~
Glycopyrronium Approved for the Treatment of Excessive Underarm Sweating
June 28th: The FDA has approved Glycopyrronium (QbrexaTM) for the treatment of primary axillary hyperhidrosis – excessive underarm sweating - in patients ages 9 and older.
Rapid Onset, Long-Acting Aripiprazole Approved for Psychosis
June 29th: The United States FDA has approved a quicker-onset formulation of the long-acting injectable antipsychotic agent aripiprazole lauroxil (Aristada Initio) that does not require 3 weeks of orally dosed aripiprazole before therapeutic onset.
Incobotulinumtoxin A Approved for Excessive Drooling
July 4th: The United States FDA has approved injectable incobotulinumtoxin A (a neuronal acetylcholine release inhibitor) previously approved for cervical dystonia and blepharospasm, for the treatment of sialorrhea, or excessive drooling.
Coffee Drinking Again Associated with Decreased Mortality
July 5th, 2018: Coffee drinking was associated with decreased mortality over 10 years. Mortality benefits were observed in participants drinking 1 – 8 or more cups per day, ground coffee, decaffeinated coffee, and instant coffee. Prospective observational (498,134 participants).
~ Clinical Trials: New Horizons ~
Ravelizumab for PNH Effective When Dosed Q8 Weeks
June 17th, EHA Conference: A new C5 inhibitor, ravelizumab, has demonstrated non-inferiority to eculizumab in treating paroxysmal nocturnal hemoglobinuria when dosed intravenously at 8 week intervals. Eculizumab is currently administered every two weeks. RCT (245 patients).
Cabozantinib, Novel Tyrosine Kinase Inhibitor, Improves Survival in Hepatocellular Carcinoma
July 5th, NEJM: Oral, once daily cabozantinib (VEGF receptor, MET and AXL tyrosine kinase inhibitor) extended median survival in patients with advanced hepatocellular carcinoma by 2.2 months relative to placebo. RCT, Phase III Clinical Trial (707 patients).
Patisiran, Hepatically Targeted RNAi Agent, Improves Outcomes in Hereditary Transthyretin Amyloidosis
July 5th, NEJM: Patisiran, an interference-RNA therapy that reduces expression of the transthyretin protein, improves clinical outcomes of hereditary transthyretin amyloidosis, including gait speed and polyneuropathy symptoms. RCT, Phase III Clinical Trial (225 patients).
Quizartinib, FLT3 Inhibitor, Improves Survival in Refractory AML
June 16th, EHA Meeting: A selective tyrosine kinase inhibitor quizartinib (fms-like tyrosine kinase 3 - FLT3 – inhibitor) has shown efficacy in a subset of relapsed/refractory acute myeloid leukemia patients with FLT3 mutations. Median overall survival was 1.5 months longer in the quizartinib group than the standard chemotherapy group. RCT (367 patients) – QuANTUM-R trial.
~ Clinical Research ~
Ramelteon May Lower Delirium Risk & ICU Duration of Stay
July 5th, Journal CCM: Ramelteon (melatonin receptor agonist often used as a sleep aid) given nightly to patients in intensive care decreased risk of delirium and may shorten ICU length of stay. RCT (88 participants).
Increased Diabetes Risk Associated with Oral Contraceptive Use
June 24th, ADA Meeting: Past use of oral contraceptives for > 6 months was associated with a 1/3 higher risk of insulin resistanse and diabetes in postmenopausal women. Observational Retrospective (6554 participants)
Antibiotic Use Before, During, and After Pregnancy Associated with Childhood Asthma Risk
July 4th, European Respiratory Journal: Maternal antibiotic use during the 9 months before beginning of pregnancy, during the pregnancy, and for 9 months after delivery was associated with a 23% increased risk of childhood asthma. Observational retrospective (213,661 mother-child dyads).
Prenatal Exposure to Folic Acid May Protect Against Later Psychosis
July 3rd, JAMA Psychiatry: Alterations in cortical development and, subsequently, decreased incidence of psychosis-spectrum disorders were observed following widespread folic acid grain fortification in the United States during the 1990’s. Observational retrospective (292 participants).
Liraglutide Lowers HbA1c More Than Bolus Insulin When HbA1c Very High
July 4th, ADA Meeting: Liraglutide (GLP-1 agonist) + metformin + basal insulin was more effective at lowering HbA1c levels over 6 months than bolus insulin + metformin + basal insulin in patients with baseline HbA1c > 10%. RCT, SIMPLE Trial (120 patients).
IVIg Speeds Recovery in Childhood ITP
June 26th, Journal Blood: Intravenous immunoglobulin (IVIg) treatment of children with newly diagnosed immune thrombocytopenia (ITP) resulted in increased complete response rate and a 36% lower likelihood of developing chronic ITP than in children not receiving IVIg. RCT (206 participants).
First Oral Formulation of GLP-1 Agonist Lowers HbA1c
June 25th, ADA Meeting: The first oral GLP-1 agonist, a novel formulation of semaglutide, has produced a median reduction in HbA1c of 1.5% and 4.3 kg of weight loss in patients with diabetes mellitus type II after 26 weeks of treatment. RCT, PIONEER-1 trial (703 participants).
Metformin Not Associated with Lactic Acidosis in Diabetic Patients with Kidney Disease
July 2nd, JAMA Internal Medicine: Two large studies have found that metformin use in patients with diabetes and eGFR between 30 to 60 mL/min/1.73 m2 was not associated with an increased incidence of metabolic acidosis. Two observational retrospective studies (75,413 and 82,017 patients, respectively).
Sodium Bicarbonate Decreased Mortality in ICU Patients with Severe Metabolic Acidosis and AKI
June 14th, The Lancet: Sodium bicarbonate decreased 28-day mortality and organ failure in patients in intensive care with severe metabolic acidosis (pH ≤ 7.20, NaHCO3 ≤ 20 mmol/L) and acute kidney injury (AKI). In patients with severe metabolic acidosis without AKI, sodium bicarbonate did not improve clinical outcomes. RCT (389 patients).
Apixaban Safer than Warfarin in Patients on Dialysis
Circulation, June 28th: Apixaban was associated with a lower risk of major bleeding in end-stage kidney disease patients compared with warfarin, as well as reductions in thromboembolism event rate and overall mortality. Retrospective observational (25,523 patients).
Norepinephrine Superior to Epinephrine In Cardiogenic Shock Following MI
July 2nd, JACC: In patients with cardiogenic shock following MI, norepinephrine had comparable effects on blood pressure and cardiac index, but was associated with lower rates of refractory shock. RCT (57 patients).
~ Reviews ~
Vitamin D Supplementation During Pregnancy Associated with Improved Infant Growth
July 2nd, JAMA Pediatrics: Vitamin D supplementation during pregnancy was associated with decreased risk of fetal/neonatal mortality, and improved infant growth. Systematic review and meta-analysis (24 RCTs, 5405 participants).
Gabapentin & Pregabalin Ineffective in Treating Low Back Pain
July 3rd, CMAJ: The anticonvulsants gabapentin and pregabalin were found to be ineffective in reducing chronic low back and lumbar radicular pain and were associated with increased risks of adverse events. Systematic Review and Meta-Analysis (15 studies, 859 patients)
MRA Therapy Associated with Improved Survival After MI (without Heart Failure)
July 2nd, JAMA Internal Medicine: Aldosterone antagonist therapy (spironolactone, eplerenone, canrenoate) following ST-segment elevation myocardial infarction in patients without heart failure (or ejection fraction < 40%) led to decreased mortality. Systematic review and meta-analysis (10 studies, 4147 patients).
Corticosteroids Associated with Improved Outcomes in Severe Community-Acquired Pneumonia
June 22nd, Annals of Emergency Medicine: Corticosteroids appear to reduce morbidity and mortality in adults with severe community-acquired pneumonia (CAP). In pediatric patients and nonsevere CAP, morbidity was improved but mortality was unaffected. Systematic review and meta-analysis (17 RCTs, 2,264 patients).
LABA + Inhaled Glucocorticoid As Safe as Inhaled Glucocorticoid Alone for Asthma
June 28th, NEJM: Combination long-acting beta agonist and inhaled glucocorticoid therapy was associated with as many adverse asthma-related events as inhaled glucocorticoid therapy alone in patients with asthma, and reduced the number of severe asthma exacerbations. Combined RCTs (4 trials, 36,010 patients)