A phase 3 trial of IV immunoglobulin for Alzheimer disease.

OBJECTIVE: We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia. METHODS: In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants. RESULTS: No beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aß42 (but not Aß40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo. CONCLUSIONS: Participants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo. CLINICALTRIALSGOV IDENTIFIER: NCT00818662. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD.

An international, multicenter, prospective study of a prothrombin complex concentrate, Prothromplex Total®, in anticoagulant reversal.

INTRODUCTION: Prothrombin complex concentrates (PCCs) are a common treatment option for the reversal of oral anticoagulation with vitamin K antagonists (VKAs). This study assessed efficacy and safety of Prothromplex Total®. MATERIALS AND METHODS: Patients (≥18 years) with acquired prothrombin complex coagulation factor deficiency (international normalized ratio [INR] ≥ 2 at screening) due to oral VKAs, requiring reversal of anticoagulation, were treated with 25, 35, or 50 IU/kg BW PCC. After infusion, efficacy was assessed for 72 ± 4 hours. Adverse events (AEs) were captured for 15 days. RESULTS: Sixty-one subjects, 48 requiring interventional procedures and 13 with acute bleeds, received a single infusion of PCC. Of 59 subjects analyzed, all achieved normalization of INR (≤ 1.3) within 30 ± 5 minutes of infusion, demonstrating effective anticoagulant reversal. IVRs of factors II, VII, IX, and X ranged from 1.12-2.03 IU/dL:IU/kg. Median INRs remained between 1.00 and 1.18 for up to 6 hours. Overall efficacy of treatment was rated "excellent" for 60 subjects. Three AEs were deemed possibly related to treatment: 1 serious AE (SAE) of acute myocardial infarction (rated severe), 1 SAE of deep vein thrombosis (rated mild), and 1 AE of pyrexia (rated mild). Thrombotic adverse events (2/61, 3.3%) reported here are comparable to rates observed in other PCC studies. CONCLUSIONS: While there is a risk of thromboembolic events following treatment with PCC products, the number of events reported here was low and could have occurred without PCC treatment. The individualized, INR-based dosing of PCC used here for VKA anticoagulant reversal produces rapid normalization of INR to ≤ 1.3 within 30 minutes.