Evidence map›Paper›PMID 23192920›Full record

Trial reportCirculation. Cardiovascular interventions2012

A randomized, controlled pilot study of autologous CD34+ cell therapy for critical limb ischemia.

Douglas W Losordo, Melina R Kibbe, Farrell Mendelsohn, William Marston, Vickie R Driver, Melhem Sharafuddin, Victoria Teodorescu, Bret N Wiechmann, Charles Thompson, Larry Kraiss and 11 more

2 registry-linked trialsAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation. Cardiovascular interventions, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 89 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 5 pooled it
–field-weighted citation impact
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.

NCT00616980 phase1 / phase2completednot on this map

Injection of Autologous CD34-Positive Cells for Improved Symptomatic Relief and Ischemic Wound Healing in Subjects With Moderate or High-Risk Critical Limb Ischemia

TypeinterventionalSponsorLosordo, Douglas, M.D.Ran2007 to 2010Enrolled28ConditionsPeripheral Artery Disease, Peripheral Vascular Disease, Critical Limb IschemiaArmsCD34-positive cells, Saline and 5% autologous plasma
NCT02915796 phase1unknown statusnot on this mapstarted 2016, after this paper: background citation

Autologous CD133(+) Cells as an Adjuvant to Below the Knee Percutaneous Transluminal Angioplasty: A Randomized Controlled Clinical Trial in Diabetic Patients With Below the Knee Critical Limb Ischemia

TypeinterventionalSponsorShanghai 10th People's HospitalRan2016 to 2018Enrolled345ConditionsPeripheral Arterial DiseaseArmsG-CSF + CD133(+) cells, G-CSF, percutaneous transluminal angioplasty (PTA), Placebo infusion
3 · Its place in the literature

Who cites it

89 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
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  9. Purified CD34EBioMedicine · 2018
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29 more citing papers are in PubMed but not listed here.

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

21 authors.

Douglas W LosordoDivision of Cardiovascular Medicine, Northwestern Memorial Hospital, Chicago, IL, USA. douglas_losordo@baxter.com
Melina R Kibbe
Farrell Mendelsohn
William Marston
Vickie R Driver
Melhem Sharafuddin
Victoria Teodorescu
Bret N Wiechmann
Charles Thompson
Larry Kraiss
Teresa Carman
Suhail Dohad
Paul Huang
Candice E Junge
Kenneth Story
Tara Weistroffer
Tina M Thorne
Meredith Millay
John Paul Runyon
Robert Schainfeld
Autologous CD34+ Cell Therapy for Critical Limb Ischemia Investigators

Funding

Small Animal Surgery and HistologyP01HL108795 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LOSORDO, DOUGLAS W · 2011 to 2015
$10.7M
Therapeutic Angiogenesis in Vascular Medicine IVR01HL053354 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KISHORE, RAJ · 1995 to 2015
$4.2M
RE-ENDOTHELIALIZATION AND RESTENOSIS IIR01HL057516 · NHLBI · STEWARD ST. ELIZABETH'S MEDICAL CENTER · PI LOSORDO, DOUGLAS W · 1997 to 2008
$3.3M
RESTENOSIS AND ENDOTHELIAL PROLIFERATIONR01HL063414 · NHLBI · STEWARD ST. ELIZABETH'S MEDICAL CENTER · PI LOSORDO, DOUGLAS W · 1999 to 2007
$2.5M
Autologous CD34+ Cell Therapy for Therapeutic Angiogenesis in Advanced PADR01HL077428 · NHLBI · STEWARD ST. ELIZABETH'S MEDICAL CENTER · PI LOSORDO, DOUGLAS W · 2006 to 2011
$2.5M
Role of Progenitor Cells in Cardiovascular MedicineR01HL080137 · NHLBI · STEWARD ST. ELIZABETH'S MEDICAL CENTER · PI LOSORDO, DOUGLAS W · 2006 to 2010
$1.9M
Novel approaches to ischemic tissue repairR01HL095874 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KISHORE, RAJ · 2009 to 2012
$1.5M
THERAPEUTIC ANGIOGENESIS IN VASCULAR MEDICINE IIR37HL053354 · NHLBI · CARITAS ST. ELIZABETH'S MEDICAL CENTER · PI ISNER, JEFFREY · 2000 to 2001
$726k
NHLBI NIH HHS HL-53354NHLBI NIH HHS HL-57516NHLBI NIH HHS HL-63414NHLBI NIH HHS HL-77428NHLBI NIH HHS HL-80137NHLBI NIH HHS HL95874NHLBI NIH HHS P01 HL108795NHLBI NIH HHS R01 HL053354NHLBI NIH HHS R01 HL057516NHLBI NIH HHS R01 HL063414NHLBI NIH HHS R01 HL077428NHLBI NIH HHS R01 HL080137NHLBI NIH HHS R01 HL095874NHLBI NIH HHS R37 HL053354PHS HHS HLPO1-108795
6 · The paper itself

Abstract

backgroundCritical limb ischemia portends a risk of major amputation of 25% to 35% within 1 year of diagnosis. Preclinical studies provide evidence that intramuscular injection of autologous CD34+ cells improves limb perfusion and reduces amputation risk. In this randomized, double-blind, placebo-controlled pilot study, we evaluated the safety and efficacy of intramuscular injections of autologous CD34+ cells in subjects with moderate or high-risk critical limb ischemia, who were poor or noncandidates for surgical or percutaneous revascularization (ACT34-CLI). METHODS AND

resultsTwenty-eight critical limb ischemia subjects were randomized and treated: 7 to 1 × 10(5) (low-dose) and 9 to 1 × 10(6) (high-dose) autologous CD34+ cells/kg; and 12 to placebo (control). Intramuscular injections were distributed into 8 sites within the ischemic lower extremity. At 6 months postinjection, 67% of control subjects experienced a major or minor amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.137). This trend continued at 12 months, with 75% of control subjects experiencing any amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.058). Amputation incidence was lower in the combined cell-treated groups compared with control group (6 months: P=0.125; 12 months: P=0.054), with the low-dose and high-dose groups individually showing trends toward improved amputation-free survival at 6 months and 12 months. No adverse safety signal was associated with cell administration.

conclusionsThis study provides evidence that intramuscular administration of autologous CD34+ cells was safe in this patient population. Favorable trends toward reduced amputation rates in cell-treated versus control subjects were observed. These findings warrant further exploration in later-phase clinical trials. CLINICAL

trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00616980.

Indexed as

Stem Cell TransplantationAgedAged, 80 and overAmputation, SurgicalAnalysis of VarianceAntigens, CD34BiomarkersCritical IllnessDisease-Free SurvivalDouble-Blind MethodFemaleHumansInjections, IntramuscularIschemiaLimb SalvageLower ExtremityAntigens, CD34Biomarkers

Identifiers

PMID23192920
PMCPMC3549397

What OpenQuestion holds

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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.