Clinical Trials – New Horizons
~ Pharmacology News ~
FDA Approves Cyclosporine Drops for Dry Eye
August 17th, Medscape: The US FDA has approved a cyclosporine A (calcineurin inhibitor used for immunosuppression) solution for the treatment of keratoconjunctivitis sicca.
FDA Expands Ivacaftor to Include Children > 12 Months with Cystic Fibrosis
August 15th, Vertex Pharmaceuticals: The FDA has expanded the indication of ivacaftor (Kalydeco) monotherapy to include children as young as 12 months with cystic fibrosis and a CFTR mutation response to ivacaftor.
FDA Approves Nivolumab for Treatment of Refractory Small Cell Lung Cancer
August 17th, FDA: The US FDA has approved intravenous nivolumab, a PD-1 checkpoint inhibitor, for the treatment of metastatic small cell lung cancer that has progressed on both first-line platinum-based chemotherapy and on a second-line agent.
FDA Expands Indication of Lenvatinib to Include Liver Cancer
August 16th, FDA: The FDA has expanded the indication of lenvatinib, a VEGF receptor inhibitor previously approved for the treatment of renal cell carcinoma and thyroid cancer, to include first-line treatment of unresectable hepatocellular carcinoma.
1/10 Surgery or Endoscopy Patients Experience Adverse Opioid Related Events
August 16th, JAMA Surgery: 10.6% of patients undergoing hospital-based surgical or endoscopic procedures were found to have a had at least one opioid-related adverse drug event (ORADE). Patients who experienced an ORADE were more likely to have worse outcomes, including higher inpatient mortality, longer length of stay, and a higher likelihood of readmission within 30 days. Observational retrospective (135,379 patients).
AHA Recommends Low-Calorie Sweetened Beverages in Some Adults, Not Children
July 30th, Circulation: The American Heart Association (AHA) issued a recommendation that low-calorie sweetened beverages should be considered in adults who consume large volumes of sugar-sweetened beverages. The organization advises against consumption of these beverages by children.
Addiction Meds Associated with Decreased Suicidality, Crime, Overdose
August 2nd, American Journal of Psychiatry: Individuals with alcohol or opioid use disorder who received naltrexone were less likely to experience accidental overdose while on treatment than during periods without treatment. Buprenorphine therapy was associated with decreased arrest rates and accidental overdose, and methadone was associated with decreased risk of suicide. Patients who received acamprosate therapy were not observed to have altered risk of suicide, overdose or arrest while receiving treatment compared to periods when they were not receiving treatment. Observational retrospective (21,218 individuals).
DDT Exposure Associated with Increased Risk of Autism
August 16th, American Journal of Psychiatry: High maternal serum levels of p,p′-DDE, a metabolite of the insecticide DDT, were associated with increased risk of autism among offspring (odds ratio in 75th percentile of DDE levels: 1.32). Observational retrospective (778 case-control pairs).
~ Clinical Trials: New Horizons ~
PARP Inhibitor Talazoparib Extends Progression-Free Survival in BRCA+ Breast Cancer
August 15th, NEJM: Patients with advanced breast cancer and germline BRCA1/2 mutations were observed to have a 3 month longer progression-free survival when treated with the poly(adenosine diphosphate–ribose) inhibitor talazoparib as those treated with standard single-agent therapy (capecitabine, eribulin, gemcitabine, or vinorelbine). RCT (431 patients).
Anti-CD4 Antibody Ibalizumab Demonstrates Efficacy Against Drug-Resistant HIV
August 16th, NEJM: In patients with multi-drug resistant HIV, the humanized monoclonal IgG4 anti-CD4 antibody was associated with a significant viral load reduction in 83% of patients. Open-label Phase III, not controlled (31 patients completed trial).
Botulinum Toxin Improves Urinary Incontinence in Multiple Sclerosis
August 14th, Journal Neurology: Intradetrusor injections of onabotulinumtoxinA in patients with multiple sclerosis were found to reduce urinary incontinence (-3.3 fewer episodes per day) compared with placebo injections (-1.1 fewer episodes per day). RCT, double-blind phase III (144 patients).
Fasinumab Shows Efficacy in Osteoarthritis of Knee, Hip
August 16th, Teva/Regeneron: Fasinumab, a monoclonal anti-nerve growth factor antibody, was associated with decreased pain in patients with osteoarthritis of the knee and hip, compared with placebo. RCT, Phase III (646 patients).
~ Clinical Research ~
Levetiracetam Seizure Prophylaxis After Intracerebral Hemorrhage Associated with Worse Outcomes
August 16th, Critical Care Medicine: Levetiracetam seizure prophylaxis in hospitalized patients with intracerebral hemorrhage was associated with decreased cognitive function-related quality of life, and an increased risk of lobar hematoma, compared with patients who received no seizure prophylaxis. Prospective observational (394 patients).
Edoxaban Associated with Lower Mortality Risk Than Warfarin in Korean Patients with Atrial Fibrillation
August 14th, JACC: In Korean patients with atrial fibrillation, edoxaban anticoagulation was associated with a 30% lower risk of stroke, decreased all-cause mortality, and a lower risk of major bleeding compared with warfarin. Observational (16,244 patients).
Oral Steroids Not Associated with Improved Hearing in Most Children with Otitis Media
August 18th, The Lancet: Administration of oral prednisolone in children with acute otitis media was associated with improved hearing in 1 out of 14 patients after 5 weeks, with no overall effect on quality of life. RCT, OSTRICH trial (389 children).
Very High and Low Sodium Intake Associated with Increased Risk of Stroke, Mortality
August 11th, The Lancet: In an epidemiological study in China, increased stroke risk was correlated with sodium intake in individuals whose sodium consumption was very high (>5g/day). Individuals in communities where salt intake was very low (<4 g/day) were also found to have an increased risk of cardiovascular events. No correlation between salt intake and stroke risk was observed in the middle tertile (mean 4.7 g/day). Observational (95,767 pariticpants).
Discontinuation of Mass Azithromycin Administration in Ethiopa Associated with Trachoma Rebound
August 14th, PLOS Medicine: Mass administration of azithromycin in Ethiopa for an additional 3 years - after an initial 4 year treatment period - led to sustained lower rates of ocular chlamydia trachomatis, but did not eliminate the disease. In subgroups where mass azithromycin was discontinued, disease rates doubled over three years. TANA II trial, re-randomization of TANA I RCT (3,938 children).
Radioactive Iodine May Not Improve Outcomes in Recurrent Papillary Thyroid Cancer
August 15th, JAMA Surgery: In patients undergoing re-operation for persistent or recurrent papillary thyroid cancer, radioactive iodine therapy did not appear to improve mortality compared with patients who received re-operation alone. Observational retrospective (102 patients).
Cetuximab + Radiation Inferior to Standard Care in HPV+ Oropharyngeal Cancer
August 14th, NIH News Release: Cetuximab, an EGFR inhibitor, + radiation was associated with worse overall and progression-free survival than the current standard of care, cisplatin + radiation, in patients with HPV+ oropharyngeal cancer. Interim analysis of Phase III RCT (987 patients).
Fludrocortisone Helps Normalize Sodium, Does Not Improve Outcomes in Tuberculous Meningitis
August 13th, JAMA Neurology: Addition of oral fludrocortisone to oral and intravenous sodium supplementation in patients with tuberculous meningitis and cerebral salt wasting was associated with earlier normalization of serum sodium levels, but was not associated with improved outcomes within 6 months. RCT (36 patients).
Patients with IBD on Anti-TNF Therapy Less Likely to Develop Parkinson’s
April 23rd/August 13th, JAMA Neurology: Although patients with inflammatory bowel disease (IBD) are more likely to develop Parkinson’s than patients without IBD, individuals with IBD who are treated with anti-tumor necrosis factor (anti-TNF) therapies are 78% less likely to develop the disease than patients with IBD who are not treated with anti-TNF drugs. Observational retrospective (144,018 patients).
SGLT-2 Inhibitors Associated with Increased Risk of Amputations
August 13th, JAMA Internal Medicine: Patients with type II diabetes who received SGLT-2 inhibitor therapy were more likely than patients who used older antidiabetic drugs (e.g., sulfonylurea, metformin hydrochloride, or thiazolidinediones) to undergo lower extremity amputation. SGLT-2 use was not associated with a higher rate of amputation compared with DPP-I and GLP-I inhibitor use. Observational retrospective (953,906 individuals).
Benzodiazepine Use Associated with Increased Risk for Alzheimer’s Disease
May 31st, Acta Psychiatra Scandinavica: Benzodiazepine use was associated with a 6% increased risk of Alzheimer’s disease in a Finnish population. Observational retrospective (353,581 participants).
Thiamine in Septic Shock Associated with Lower Mortality
June 18th, Journal CCM: Intravenous thiamine administration in ICU patients with septic shock was associated with an increased likelihood of lactate clearance and a 33% decrease in 28-day mortality compared with patients who did not receive thiamine. Observational retrospective (269 patients).
TNF Inhibitors in Rheumatoid Arthritis Not Associated with Increased Risk of Cancer Recurrence
August 14th, Annals of Internal Medicine: Tumor necrosis factor inhibitors (TNFi) prescribed for patients with rheumatoid arthritis (RA) who had previously received a cancer diagnosis did not appear to increase the risk of cancer recurrence compared with RA patients who were not given TNFi. Observational (467 patients).
Fetal Quetiapine Exposure Not Associated with Increased Risk of Malformations
August 16th, American Journal of Psychiatry: Maternal first-trimester exposure to quetiapine was not associated with an increased risk of fetal malformations relative to unexposed patients. Observational prospective (357 eligible participants).
Remifentanil More Effective Than Pethidine in Reducing Epidural Use During Delivery
August 13th, The Lancet: Intravenous remifentanil, a short-acting opioid, decreased the number of epidural conversions during labor and delivery by 52% relative to intramuscular pethidine (meperidine, Demerol), a commonly used opioid for labor and delivery anesthesia in the UK. RCT (201 patients).
Skepticism, Stigma Top Barriers to Alcohol Use Disorder Treatment
August 17th, Journal of General Internal Medicine: Among patients with alcohol use disorder, 21% reported wanting treatment while <15% received treatment. Among those who did not receive treatment, nearly half reported skepticism about efficacy and concerns about stigma as barriers to pursuing treatment. Observational, survey (5547 respondents, 555 with alcohol use disorder).
~ Reviews ~
Corticosteroids May Decrease Mortality in Sepsis
August 16th, Critical Care Medicine: Critically ill patients with sepsis who received intravenous corticosteroids were found to have a lower risk of death (relative risk 0.93) in the short term (28-31 days), but had a 16% higher rate of hyperglycemia and an increased risk of neuromuscular weakness. Systematic review and meta-analysis (42 RCTs, 10,194 patients).
Higher-Dose Rivaroxaban Associated with Increased Risk of Intracranial Hemorrhage
August 13th, JAMA Neurology: Patients who received 15-20 mg daily doses of rivaroxaban, a non-vitamin K antagonist oral anticoagulant, for stroke prevention were more likely to develop intracranial hemorrhage than patients who used only aspirin, a lower (10 mg) daily dose of rivaroxaban, or 5 mg of apixaban. Systematic review and meta-analysis (5 RCTs, 39,398 patients).
Vitamin D Only Dietary Supplement At This Time with Clear Benefit in Multiple Sclerosis
April 23rd/August 13th, JAMA Neurology: Although large trials of other dietary modifications and supplements (e.g., biotin) are currently being conducted, current data supports only vitamin D for routine supplementation in patients with multiple sclerosis. Literature review.
Both Low and High Intake of Carbohydrates Associated with Increased Mortality
August 16th, The Lancet Public Health: In a prospective cohort study and meta-analysis, individuals who report both low carbohydrate intake (<40% of energy derived from carbohydrates) and high carbohydrate intake (>70% of calories derived from carbs) had a higher 25-year mortality than those who reported 50-55% of their energy as coming from carbohydrate sources. Prospective cohort study (15,428 participants) and meta-analysis (432,179 participants).