Evidence map›Paper›PMID 24252058›Full record

Trial reportHaemophilia : the official journal of the World Federation of Hemophilia2014

Correlation between endogenous VWF:Ag and PK parameters and bleeding frequency in severe haemophilia A subjects during three-times-weekly prophylaxis with rFVIII-FS.

S Lalezari, U Martinowitz, J Windyga, M M Enriquez, H Delesen, L Schwartz, I Scharrer

Erratum issued Registry-linked trialOpen access · hybridAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Haemophilia : the official journal of the World Federation of Hemophilia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04303936 (PHYSICAL ACTIVITY AND FVIII CLEARANCE), which is not on this map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
1.2field-weighted citation impact, top 21% 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.

NCT04303936 naunknown statusnot on this mapstarted 2020, after this paper: background citation

Physical activity and fviii clearance: relevance for personalized therapy in severe haemophilia a

TypeinterventionalSponsorCatholic University of the Sacred HeartRan2020 to 2020Enrolled20ConditionsHemophilia AArmsSenseWear® armband device
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.

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  14. Biological mechanisms underlying inter-individual variation in factor VIII clearance in haemophilia.Haemophilia : the official journal of the World Federation of Hemophilia · 2020
    Review
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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

7 authors at 5 institutions in 4 countries.

S LalezariNational Hemophilia Center, Chaim Sheba Medical Center, Tel Hashomer, Israel.
U Martinowitz
J Windyga
M M Enriquez
H Delesen
L Schwartz
I Scharrer
Bayer (Germany) · DESheba Medical Center · ILBayer (United States) · USInstytut Hematologii i Transfuzjologi · PLJohannes Gutenberg University Mainz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Patients with severe haemophilia A experience frequent and spontaneous bleeding, causing debilitating damage to joints and decreasing quality of life. Prophylaxis with factor VIII (FVIII) reduces joint damage if initiated early. Circulating FVIII levels may be influenced by endogenous von Willebrand factor (VWF), a chaperone protein that binds and stabilizes FVIII. The aim of this study was to determine whether endogenous VWF antigen (VWF:Ag) levels are correlated with FVIII pharmacokinetic (PK) parameters and clinical outcomes in patients with severe haemophilia A. Previously treated, non-inhibitor patients in a multinational, randomized, double-blind, Ph II study received prophylaxis with once-weekly BAY 79-4980 (35 IU kg(-1)) or thrice-weekly recombinant sucrose-formulated FVIII (rFVIII-FS; 25 IU kg(-1)). PK parameters were evaluated at weeks 1 and 26. The number of bleeds per patient during the study was captured as part of the core efficacy endpoint. Spearman rank correlations assessed relationships of VWF:Ag levels with patient age, PK and annualized bleeding rate. Of 131 study patients (aged 13-64 years; BAY 79-4980, n = 63; rFVIII-FS, n = 68), 27 (21%; n = 15 and 12 respectively) were evaluable for PK assessment. Baseline VWF:Ag levels correlated with patient age (P < 0.0001). There was no significant difference in PK results between treatments; thus, PK parameters and VWF levels of all patients were analysed together. AUC(norm) and T1/2 significantly increased with increased VWF:Ag (P < 0.001); clearance significantly decreased with increased VWF:Ag (P = 0.002). Annualized bleeding rate in patients treated with 3× per week rFVIII-FS significantly correlated with VWF:Ag and age (P = 0.038 and 0.021 respectively). PK parameters as well as the clinical outcome significantly correlated with endogenous VWF:Ag. The improved clinical outcome in subjects with high VWF:Ag levels may be explained by VWF:Ag influence on FVIII PK.

Indexed as

PremedicationAdolescentAdultAgedAge FactorsBlood Coagulation TestsDrug Administration ScheduleEnzyme-Linked Immunosorbent AssayFactor VIIIHemophilia AHemorrhageHumansMaleMiddle AgedSeverity of Illness IndexSucroseFactor VIIIrecombinant FVIII, sugar formulatedSucrosevon Willebrand Factoragefactor VIIIpharmacokineticsvon Willebrand factor

Identifiers

PMID24252058
PMCPMC4233978
OpenAlexW2037436415

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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.