Randomized, Double‐Blind Controlled Phase 3 Trial Comparing the Immunogenicity of High‐Dose and Standard‐Dose Influenza Vaccine in Adults 65 Years of Age and Older

Abstract Passive surveillance data had signaled the possibility of gastrointestinal adverse events occurring after the administration of high-dose inactivated influenza vaccine (IIV-HD). However, in a large, prospective randomized clinical trial, rates of serious gastrointestinal events were no greater among IIV-HD recipients than among those who received a standard-dose influenza vaccine.

Download Full-text

Immunogenicity of high-dose influenza vaccination in patients with primary central nervous system malignancy

Neuro-Oncology Practice ◽

10.1093/nop/npx035 ◽

2018 ◽

Vol 5 (3) ◽

pp. 176-183

Author(s):

Roy E Strowd ◽

Gregory Russell ◽

Fang-Chi Hsu ◽

Annette F Carter ◽

Michael Chan ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Influenza Vaccine ◽

Elderly Patients ◽

Influenza Vaccination ◽

Standard Dose ◽

High Grade Glioma ◽

Cns Lymphoma ◽

High Dose ◽

Central Nervous System Malignancy

Abstract Background For cancer patients, rates of influenza-associated hospitalization and death are 4 times greater than that of the general population. Previously, we reported reduced immunogenicity to the standard-dose influenza vaccine in patients with central nervous system malignancy. In other poorly responding populations (eg, elderly patients), high-dose vaccination has improved efficacy and immunogenicity. Methods A prospective cohort study was designed to evaluate the immunogenicity of the Fluzone® high-dose influenza vaccine in brain tumor patients. Data on diagnosis, active oncologic treatment, and immunologic status (eg, CD4 count, CD8 count, CD4:CD8 ratio) were collected. All patients received the high-dose vaccine (180 µg). Hemagglutination inhibition titers were measured at baseline, day 28, and 3 months following vaccination to determine seroconversion (≥4-fold rise) and seroprotection (titer ≥1:40), which were compared to our prior results. Results Twenty-seven patients enrolled. Diagnoses included high-grade glioma (85%), CNS lymphoma (11%), and meningioma (4%). Treatment at enrollment included glucocorticoids (n = 8, 30%), radiation (n = 2, 7%), and chemotherapy (n = 9, 33%). Posttreatment lymphopenia (PTL, CD4 ≤ 200) was observed in 4 patients (15%). High-dose vaccination was well tolerated with no grade III-IV toxicity. Overall, seroconversion rates for the A/H1N1, A/H3N2, and B vaccine strains were significantly higher than in our prior study: 65% vs 37%, 69% vs 23%, and 50% vs 23%, respectively (all P < .04). Seroconversion was universally poor in patients with PTL. While seroprotection at 3 months declined in our prior study, no drop was observed following high-dose vaccination in this cohort. Conclusions The immunologic response to HD influenza vaccination was higher in this cohort than standard-dose influenza vaccination in our prior report. These findings mirror those in elderly patients where high-dose vaccination is the standard of care and raise the possibility of an immunosenescence phenotype.

Download Full-text

Randomized Controlled Trial of High-Dose Intradermal Versus Standard-Dose Intramuscular Influenza Vaccine in Organ Transplant Recipients

American Journal of Transplantation ◽

10.1111/ajt.12149 ◽

2013 ◽

Vol 13 (4) ◽

pp. 1026-1033 ◽

Cited By ~ 54

Author(s):

A. Baluch ◽

A. Humar ◽

D. Eurich ◽

A. Egli ◽

A. Liacini ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Influenza Vaccine ◽

Standard Dose ◽

Controlled Trial ◽

Organ Transplant ◽

High Dose ◽

Transplant Recipients ◽

Organ Transplant Recipients ◽

Randomized Controlled

Download Full-text

Double-Blind, Randomized, Placebo-Controlled Phase II Dose-Finding Study To Evaluate High-Dose Rifampin for Tuberculous Meningitis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01014-18 ◽

2018 ◽

Vol 62 (12) ◽

Cited By ~ 19

Author(s):

S. Dian ◽

V. Yunivita ◽

A. R. Ganiem ◽

T. Pramaesya ◽

L. Chaidir ◽

...

Keyword(s):

Adverse Events ◽

Phase Ii ◽

Tuberculous Meningitis ◽

Standard Dose ◽

Geometric Mean ◽

Phase Iii ◽

High Dose ◽

Treatment Area ◽

Double Blind ◽

Time Curve

ABSTRACT High doses of rifampin may help patients with tuberculous meningitis (TBM) to survive. Pharmacokinetic pharmacodynamic evaluations suggested that rifampin doses higher than 13 mg/kg given intravenously or 20 mg/kg given orally (as previously studied) are warranted to maximize treatment response. In a double-blind, randomized, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450 mg, 900 mg, or 1,350 mg (10, 20, and 30 mg/kg) oral rifampin combined with other TB drugs for 30 days. The endpoints included pharmacokinetic measures, adverse events, and survival. A double and triple dose of oral rifampin led to 3- and 5-fold higher geometric mean total exposures in plasma in the critical early days (2 ± 1) of treatment (area under the concentration-time curve from 0 to 24 h [AUC0–24], 53.5 mg · h/liter versus 170.6 mg · h/liter and 293.5 mg · h/liter, respectively; P < 0.001), with proportional increases in cerebrospinal fluid (CSF) concentrations and without an increase in the incidence of grade 3 or 4 adverse events. The 6-month mortality was 7/20 (35%), 9/20 (45%), and 3/20 (15%) in the 10-, 20-, and 30-mg/kg groups, respectively (P = 0.12). A tripling of the standard dose caused a large increase in rifampin exposure in plasma and CSF and was safe. The survival benefit with this dose should now be evaluated in a larger phase III clinical trial. (This study has been registered at ClinicalTrials.gov under identifier NCT02169882.)

Download Full-text