Evidence map›Paper›PMID 26346408›Full record

Trial reportTransplant infectious disease : an official journal of the Transplantation Society2015

Voriconazole therapeutic drug monitoring: results of a prematurely discontinued randomized multicenter trial.

D Neofytos, D Ostrander, S Shoham, M Laverdiere, J Hiemenz, H Nguyen, W Clarke, L Brass, N Lu, K A Marr

Open access · greenAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Transplant infectious disease : an official journal of the Transplantation Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Review
  3. Evaluation of voriconazole therapeutic drug monitoring in malignant hematology patients.Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners · 2025
    Article
  4. Review
  5. Article
  6. Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2021
    Article
  7. Article
  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

D NeofytosSchool of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.
D OstranderSchool of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.
S ShohamSchool of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.
M LaverdiereHopital Maisonneuve-Rosemont, University of Montreal, Montreal, Quebec, Canada.
J HiemenzUniversity of Florida, Gaineville, Florida, USA.
H NguyenUniversity of Pittsburgh, Pittsburgh, Pennsylvania, USA.
W ClarkeSchool of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.
L BrassSchool of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.
N LuSchool of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.
K A MarrSchool of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.
Johns Hopkins University · USHôpital Maisonneuve-Rosemont · CAUniversity of Florida Health · USUniversity of Pittsburgh · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Patient Oriented Research in Transplant and Oncology IDK24AI085118 · NIAID · JOHNS HOPKINS UNIVERSITY · PI MARR, KIEREN A. · 2010 to 2014
$995k
NCI NIH HHS P30 CA006973NIAID NIH HHS K24 AI085118
6 · The paper itself

Abstract

backgroundVoriconazole (VOR) levels are highly variable, with potential implications to both efficacy and safety. We hypothesized that VOR therapeutic drug monitoring (TDM) will decrease the incidence of treatment failures and adverse events (AEs).

methodsWe initiated a prospective, randomized, non-blinded multicenter study to compare clinical outcomes in adult patients randomized to standard dosing (clinician-driven) vs. TDM (doses adjusted based on levels). VOR trough levels were obtained on day 5, 14, 28, and 42 (or at completion of drug; ± 3 days). Real-time dose adjustments were made to maintain a range between 1-5 μg/mL on the TDM-arm, while levels were assessed retrospectively in the standard-arm. Patient questionnaires were administered to assess subjective AEs.

resultsThe study was discontinued prematurely, after 29 patients were enrolled. Seventeen (58.6%) patients experienced 38 AEs: visual changes (22/38, 57.9%), neurological symptoms (13/38, 34.2%), and liver abnormalities (3/38, 7.9%). VOR was discontinued in 7 (25%) patients because of an AE (4 standard-arm, 3 TDM-arm). VOR levels were frequently out of range in the standard-arm (8 tests >5 μg/mL; 9 tests <1 μg/mL). Three dose changes occurred in the TDM-arm for VOR levels <1 μg/mL. Levels decreased over time in the standard-arm, with mean VOR levels lower at end of therapy compared to TDM (1.3 vs. 4.6 μg/mL, P = 0.008).

conclusionsVOR TDM has become widespread clinical practice, based on known variability in drug levels, which impaired accrual in this study. Although comparative conclusions are limited, observations of variability and waning levels over time support TDM.

Indexed as

Drug MonitoringAdultAgedAged, 80 and overAntifungal AgentsDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedVoriconazoleAntifungal AgentsVoriconazoletherapeutic drug monitoringtransplant monitoringvoriconazole

Identifiers

PMID26346408
PMCPMC4715512
OpenAlexW1487933470

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.