Evidence map›Paper›PMID 26307570›Full record

Trial reportJournal of the American Heart Association2015

Infusion of Reconstituted High-Density Lipoprotein, CSL112, in Patients With Atherosclerosis: Safety and Pharmacokinetic Results From a Phase 2a Randomized Clinical Trial.

Pierluigi Tricoci, Denise M D'Andrea, Paul A Gurbel, Zhenling Yao, Marina Cuchel, Brion Winston, Robert Schott, Robert Weiss, Michael A Blazing, Louis Cannon and 6 more

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

Trial report in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01499420 (A Phase 2a, Multi-center, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of a Single Intravenous Infusion of CSL112 in Patients With Stable Atherothrombotic Disease), which is not on this map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
13.6field-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.

NCT01499420 phase2completednot on this map

A Phase 2a, Multi-center, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of a Single Intravenous Infusion of CSL112 in Patients With Stable Atherothrombotic Disease

TypeinterventionalSponsorCSL LimitedRan2012 to 2013Enrolled45ConditionsStable Atherothrombotic DiseaseArmsCSL112 (reconstituted high density lipoprotein), Placebo
3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.

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  14. Residual risks and evolving atherosclerotic plaques.Molecular and cellular biochemistry · 2023
    Review
  15. Nanomedicine for Diagnosis and Treatment of Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 10 institutions in 2 countries.

Pierluigi TricociDuke Clinical Research Institute, Durham, NC (P.T., M.A.B., J.H.A.).
Denise M D'AndreaCSL Behring, King of Prussia, PA (D.M.A., Z.Y., C.L.S., S.D.W.).
Paul A GurbelSinai Center for Thrombosis Research, Sinai Hospital of Baltimore and Johns Hopkins University School of Medicine, Baltimore, MD (P.A.G.).
Zhenling YaoCSL Behring, King of Prussia, PA (D.M.A., Z.Y., C.L.S., S.D.W.).
Marina CuchelUniversity of Pennsylvania, Philadelphia, PA (M.C.).
Brion WinstonBlack Hills Cardiovascular Research, Rapid City, SD (B.W.).
Robert SchottdiaDexus, Inc., San Francisco, CA (R.S.).
Robert WeissMaine Research Associates, Auburn, ME (R.W.).
Michael A BlazingDuke Clinical Research Institute, Durham, NC (P.T., M.A.B., J.H.A.).
Louis CannonCardiac and Vascular Research Center of Northern Michigan, Petoskey, MI (L.C.).
Alison BaileyGill Heart Institute, University of Kentucky, Lexington, KY (A.B.).
Dominick J AngiolilloUniversity of Florida College of Medicine-Jacksonville, Jacksonville, FL (D.J.A.).
Andreas GilleCSL Limited, Parkville, Victoria, Australia (A.G.).
Charles L ShearCSL Behring, King of Prussia, PA (D.M.A., Z.Y., C.L.S., S.D.W.).
Samuel D WrightCSL Behring, King of Prussia, PA (D.M.A., Z.Y., C.L.S., S.D.W.).
John H AlexanderDuke Clinical Research Institute, Durham, NC (P.T., M.A.B., J.H.A.).
CSL (United States) · USClinical Research Institute · USCardiac And Vascular Research Center Of Northern Michigan · USCSL (Australia) · AUDiazyme (United States) · USFlorida College · USMaine Research Associates · USSinai Hospital · USUniversity of Kentucky · USUniversity of Pennsylvania · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCSL112 is a new formulation of human apolipoprotein A-I (apoA-I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double-blind, multicenter, dose-ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease. METHODS AND

resultsPatients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2-hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations >3× upper limits of normal and study drug-related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA-I plasma concentration and measures of the ability of serum to promote cholesterol efflux from cells ex vivo. Of 45 patients randomized, 7, 12, and 14 received 1.7-, 3.4-, and 6.8-g CSL112, respectively, and 11 received placebo. There were no clinically significant elevations (>3× upper limit of normal) in alanine aminotransferase or aspartate aminotransferase. Adverse events were nonserious and mild and occurred in 5 (71%), 5 (41%), and 6 (43%) patients in the CSL112 1.7-, 3.4-, and 6.8-g groups, respectively, compared with 3 (27%) placebo patients. The imbalance in adverse events was attributable to vessel puncture/infusion-site bruising. CSL112 resulted in rapid (T(max)≈2 hours) and dose-dependent increases in apoA-I (145% increase in the 6.8-g group) and total cholesterol efflux (up to 3.1-fold higher than placebo) (P<0.001).

conclusionsCSL112 infusion was well tolerated in patients with stable atherosclerotic disease. CSL112 immediately raised apoA-I levels and caused a rapid and marked increase in the capacity of serum to efflux cholesterol. This potential novel approach for the treatment of atherosclerosis warrants further investigation. CLINICAL

trial registrationURL: http://www.ClinicalTrials.gov. Unique identifier: NCT01499420.

Indexed as

AdultAgedApolipoprotein A-IAtherosclerosisBiomarkersCholesterolCoronary Artery DiseaseDouble-Blind MethodFemaleHumansHypolipidemic AgentsInfusions, IntravenousLipoproteins, HDLMaleMiddle AgedPeripheral Vascular DiseasesAPOA1 protein, humanApolipoprotein A-IBiomarkersCholesterolCSL112Hypolipidemic AgentsLipoproteins, HDLapolipoproteinatherosclerosisclinical trialcoronary diseaseplaque

Identifiers

PMID26307570
PMCPMC4599471
OpenAlexW2154023449

What OpenQuestion holds

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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.