Evidence map›Paper›PMID 22336189›Full record

Trial reportLancet (London, England)2012

Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial.

Raj R Makkar, Rachel R Smith, Ke Cheng, Konstantinos Malliaras, Louise Ej Thomson, Daniel Berman, Lawrence Sc Czer, Linda Marbán, Adam Mendizabal, Peter V Johnston and 5 more

Registry-linked trialAbstract readClinical Trial, Phase IMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Lancet (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00893360 (A Phase I Randomized, Dose Escalation Study of the Safety and Efficacy of Intracoronary Delivery of Cardiosphere-Derived Stem Cells in Patients With Ischemic Left Ventricular Dysfunction and a Recent Myocardial Infarction), which is not on this map. Cited by 684 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
684citing papers in PubMed, 5 pooled it
183.6field-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.

NCT00893360 phase1completednot on this map

A Phase I Randomized, Dose Escalation Study of the Safety and Efficacy of Intracoronary Delivery of Cardiosphere-Derived Stem Cells in Patients With Ischemic Left Ventricular Dysfunction and a Recent Myocardial Infarction

TypeinterventionalSponsorCedars-Sinai Medical CenterRan2009 to 2012Enrolled31ConditionsRecent Myocardial Infarction, Ventricular DysfunctionArmsAutologous stem cell infusion
3 · Its place in the literature

Who cites it

684 citing papers in PubMed, 5 syntheses or guidelines pooled it, 1,404 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Raj R MakkarCedars-Sinai Heart Institute, Los Angeles, CA, USA.
Rachel R SmithCedars-Sinai Heart Institute, Los Angeles, CA, USA.
Ke ChengCedars-Sinai Heart Institute, Los Angeles, CA, USA.
Konstantinos MalliarasCedars-Sinai Heart Institute, Los Angeles, CA, USA.
Louise Ej ThomsonCedars-Sinai Heart Institute, Los Angeles, CA, USA.
Daniel BermanCedars-Sinai Heart Institute, Los Angeles, CA, USA.
Lawrence Sc CzerCedars-Sinai Heart Institute, Los Angeles, CA, USA.
Linda MarbánCedars-Sinai Heart Institute, Los Angeles, CA, USA.
Adam MendizabalThe EMMES Corporation, Rockville, MD, USA.
Peter V JohnstonThe Johns Hopkins University, Baltimore, MD, USA.
Stuart D RussellThe Johns Hopkins University, Baltimore, MD, USA.
Karl H SchuleriThe Johns Hopkins University, Baltimore, MD, USA.
Albert C LardoThe Johns Hopkins University, Baltimore, MD, USA.
Gary GerstenblithThe Johns Hopkins University, Baltimore, MD, USA.
Eduardo MarbánCedars-Sinai Heart Institute, Los Angeles, CA, USA. Electronic address: eduardo.marban@csmc.edu.
Cedars-Sinai Medical Center · USJohns Hopkins University · USEmmes (United States) · US

Funding

Mesenchymal Stem Cell CardiomyoplastyU54HL081028 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MARBAN, EDUARDO · 2005 to 2009
$12.1M
NHLBI NIH HHS U54 HL081028
6 · The paper itself

Abstract

backgroundCardiosphere-derived cells (CDCs) reduce scarring after myocardial infarction, increase viable myocardium, and boost cardiac function in preclinical models. We aimed to assess safety of such an approach in patients with left ventricular dysfunction after myocardial infarction.

methodsIn the prospective, randomised CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial, we enrolled patients 2-4 weeks after myocardial infarction (with left ventricular ejection fraction of 25-45%) at two medical centres in the USA. An independent data coordinating centre randomly allocated patients in a 2:1 ratio to receive CDCs or standard care. For patients assigned to receive CDCs, autologous cells grown from endomyocardial biopsy specimens were infused into the infarct-related artery 1·5-3 months after myocardial infarction. The primary endpoint was proportion of patients at 6 months who died due to ventricular tachycardia, ventricular fibrillation, or sudden unexpected death, or had myocardial infarction after cell infusion, new cardiac tumour formation on MRI, or a major adverse cardiac event (MACE; composite of death and hospital admission for heart failure or non-fatal recurrent myocardial infarction). We also assessed preliminary efficacy endpoints on MRI by 6 months. Data analysers were masked to group assignment. This study is registered with ClinicalTrials.gov, NCT00893360.

findingsBetween May 5, 2009, and Dec 16, 2010, we randomly allocated 31 eligible participants of whom 25 were included in a per-protocol analysis (17 to CDC group and eight to standard of care). Mean baseline left ventricular ejection fraction (LVEF) was 39% (SD 12) and scar occupied 24% (10) of left ventricular mass. Biopsy samples yielded prescribed cell doses within 36 days (SD 6). No complications were reported within 24 h of CDC infusion. By 6 months, no patients had died, developed cardiac tumours, or MACE in either group. Four patients (24%) in the CDC group had serious adverse events compared with one control (13%; p=1·00). Compared with controls at 6 months, MRI analysis of patients treated with CDCs showed reductions in scar mass (p=0·001), increases in viable heart mass (p=0·01) and regional contractility (p=0·02), and regional systolic wall thickening (p=0·015). However, changes in end-diastolic volume, end-systolic volume, and LVEF did not differ between groups by 6 months.

interpretationWe show intracoronary infusion of autologous CDCs after myocardial infarction is safe, warranting the expansion of such therapy to phase 2 study. The unprecedented increases we noted in viable myocardium, which are consistent with therapeutic regeneration, merit further assessment of clinical outcomes.

fundingUS National Heart, Lung and Blood Institute and Cedars-Sinai Board of Governors Heart Stem Cell Center.

Indexed as

Stem Cell TransplantationCicatrixCoronary VesselsFemaleHeartHumansInfusions, Intra-ArterialMagnetic Resonance ImagingMaleMiddle AgedMyocardial InfarctionMyocardiumRegenerationStroke VolumeTransplantation, AutologousVentricular Dysfunction, Left

Identifiers

PMID22336189
PMCPMC4326004
OpenAlexW2144327104

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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.