Evidence map›Paper›PMID 26430171›Full record

Trial reportHaematologica2015

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib.

Andrew H Lipsky, Mohammed Z H Farooqui, Xin Tian, Sabrina Martyr, Ann M Cullinane, Khanh Nghiem, Clare Sun, Janet Valdez, Carsten U Niemann, Sarah E M Herman and 7 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Haematologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01500733 (A Phase II Study of PCI-32765 for Patients With Chronic Lymphocytic Leukemia), which is not on this map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
9.7field-weighted citation impact, top 1% 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.

NCT01500733 phase2active not recruitingnot on this map

A Phase II Study of PCI-32765 for Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Who Need Therapy and Are Older Than 65 or Have a 17p Deletion

TypeinterventionalSponsorNational Heart, Lung, and Blood Institute (NHLBI)Ran2012 to 2034Enrolled86ConditionsLeukemia, Leukemia, Lymphocytyc, CLL (Chronic Lymphocytic Leukemia), SLL (Small Lymphocytic Lymphoma)ArmsPCI 32765
3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 167 citations in OpenAlex.

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25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 1 country.

Andrew H LipskyHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA Department of Internal Medicine, Montefiore Medical Center, Bronx, New York, NY, USA.
Mohammed Z H FarooquiHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Xin TianOffice of Biostatistics Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Sabrina MartyrHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Ann M CullinaneDepartment of Laboratory Medicine, NIH Clinical Center, Bethesda, MD, USA.
Khanh NghiemDepartment of Laboratory Medicine, NIH Clinical Center, Bethesda, MD, USA.
Clare SunHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Janet ValdezHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Carsten U NiemannHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Sarah E M HermanHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Nakhle SabaHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Susan SotoHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Gerald MartiHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Gulbu UzelLaboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Steve M HollandLaboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jay N LozierDepartment of Laboratory Medicine, NIH Clinical Center, Bethesda, MD, USA wiestnera@mail.nih.gov lozierjn@cc.nih.gov.
Adrian WiestnerHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA wiestnera@mail.nih.gov lozierjn@cc.nih.gov.
National Institutes of Health · USNational Heart Lung and Blood Institute · USNational Institutes of Health Clinical Center · USNational Institute of Allergy and Infectious Diseases · USMontefiore Medical Center · US

Funding

Endothelial, Platelet, & Coagulation Factor Abnormalities in Abnormal HemostasisZIACL080014 · CLC · CLINICAL CENTER · PI LOZIER, JAY · 2009 to 2017
$0k
Intramural NIH HHS
6 · The paper itself

Abstract

Ibrutinib is associated with bleeding-related adverse events of grade ≤ 2 in severity, and infrequently with grade ≥ 3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤ 2 bleeding-related adverse events in 55% of 85 patients. No grade ≥ 3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤ 2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733.

Indexed as

HemorrhageLeukemia, Lymphocytic, Chronic, B-CellPyrazolesPyrimidinesAdenineAdultAgedAged, 80 and overFactor VIIIFemaleFollow-Up StudiesHumansMaleMiddle AgedPiperidinesPlatelet AggregationAdenineF8 protein, humanFactor VIIIibrutinibPiperidinesPyrazolesPyrimidinesvon Willebrand Factor

Identifiers

PMID26430171
PMCPMC4666333
OpenAlexW2260369425

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.