Evidence mapPaperPMID 38294084Full record

Trial reportThe British journal of surgery2024

PACE: randomized, controlled, multicentre, multinational, phase III study of PLX-PAD for critical limb ischaemia in patients unsuitable for revascularization: randomized clinical trial.

Lars Norgren, Norbert Weiss, Sigrid Nikol, John C Lantis, Manesh R Patel, Robert J Hinchliffe, Holger Reinecke, Hans Dieter Volk, Petra Reinke, Gian Paolo Fadini and 5 more

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study
In one paragraph

Trial report in The British journal of surgery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03006770 (Efficacy, Tolerability and Safety of Intramuscular Injections of PLX PAD for the Treatment of Subjects With Critical Limb Ischemia), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
8.6field-weighted citation impact, top 2% 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.

NCT03006770 phase3completednot on this map

Efficacy, Tolerability and Safety of Intramuscular Injections of PLX PAD for the Treatment of Subjects With Critical Limb Ischemia (CLI) With Minor Tissue Loss Who Are Unsuitable for Revascularization

TypeinterventionalSponsorPluristem Ltd.Ran2017 to 2022Enrolled213ConditionsCritical Limb Ischemia (CLI)ArmsPLX-PAD, Placebo
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 15 citations in OpenAlex.

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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

15 authors at 10 institutions in 6 countries.

Lars NorgrenDepartment of Surgery, Örebro University and University Hospital, Örebro, Sweden.ORCID 0000-0003-2071-7132
Norbert WeissUniversity Centre for Vascular Medicine and Department of Medicine-Section Angiology, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.
Sigrid NikolDepartment of Clinical and Interventional Angiology, Asklepios Klinik St Georg, Hamburg, Germany.
John C LantisDepartment of Surgery, Mt Sinai West Hospital, Icahn School of Medicine, New York, New York, USA.
Manesh R PatelDepartment of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Robert J HinchliffeDepartment of Vascular Surgery, University of Bristol, Bristol, UK.ORCID 0000-0002-6370-0800
Holger ReineckeDepartment of Cardiology I-Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, Muenster, Germany.ORCID 0000-0002-4515-1609
Hans Dieter VolkBerlin Centre for Advanced Therapies (BeCAT) and Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Petra ReinkeBerlin Centre for Advanced Therapies (BeCAT) and Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Gian Paolo FadiniDepartment of Medicine, University of Padova, Padua, Italy and Veneto Institute of Molecular Medicine, Padua, Italy.ORCID 0000-0002-6510-2097
Racheli OfirBetalin Therapeutics, Jerusalem, Israel.
Daniel RothensteinPluri-Biotech, Haifa, Israel.
Nitsan HalevyPluri-Biotech, Haifa, Israel.
Mitko KaragjozovDepartment of Thoracic Vascular Surgery, Acibadem Sistina, Skopje, Macedonia.
John H RundbackVascular and Interventional Radiology, Holy Name Medical Centre, Teaneck, New Jersey, USA.
Charité - Universitätsmedizin Berlin · DEAcıbadem Adana Hospital · TRAsklepios Klinik St. Georg · DEDuke University · USHoly Name Medical Center · USÖrebro University Hospital · SEUniversity Hospital Carl Gustav Carus · DEUniversity Hospital Münster · DEUniversity of Bristol · GBVeneto Institute of Molecular Medicine · IT

Funding

European Union Horizon 2020 Research and Innovation Programme 733006)
6 · The paper itself

Abstract

backgroundRevascularization is the primary treatment modality for chronic limb-threatening ischaemia (CLTI), but is not feasible in all patients. PLX-PAD is an off-the-shelf, placental-derived, mesenchymal stromal cell-like cell therapy. This study aimed to evaluate whether PLX-PAD would increase amputation-free survival in people with CLTI who were not candidates for revascularization.

methodsPeople with CLTI and minor tissue loss (Rutherford 5) who were unsuitable for revascularization were entered into a randomized, parallel-group, placebo-controlled, multinational, blinded, trial, in which PLX-PAD was compared with placebo (2 : 1 randomization), with 30 intramuscular injections (0.5 ml each) into the index leg on days 0 and 60. Planned follow-up was 12-36 months, and included vital status, amputations, lesion size, pain and quality-of-life assessments, haemodynamic parameters, and adverse events.

resultsOf 213 patients enrolled, 143 were randomized to PLX-PAD and 70 to placebo. Demographics and baseline characteristics were balanced. Most patients were Caucasian (96.2%), male (76.1%), and ambulatory (85.9%). Most patients (76.6%) reported at least one adverse event, which were mostly expected events in CLTI, such as skin ulcer or gangrene. The probability of major amputation or death was similar for placebo and PLX-PAD (33 and 28.6% respectively; HR 0.93, 95% c.i. 0.53 to 1.63; P = 0.788). Revascularization and complete wound healing rates were similar in the two groups. A post hoc analysis of a subpopulation of 121 patients with a baseline haemoglobin A1c level below 6.5% showed improved 12-month amputation-free survival (HR 0.46, 0.21 to 0.99; P = 0.048).

conclusionAlthough there was no evidence that PLX-PAD reduced amputation-free survival in the entire study population, benefit was observed in patients without diabetes mellitus or whose diabetes was well controlled; this requires confirmation in further studies. Trial registration: NCT03006770 (http://www.clinicaltrials.gov); 2015-005532-18 (EudraCT Clinical Trials register - Search for 2015-005532-18).

Indexed as

Chronic Limb-Threatening IschemiaPeripheral Arterial DiseaseFemaleHumansIschemiaMalePlacentaPregnancyTreatment OutcomeVascular Surgical Procedures

Identifiers

PMID38294084
PMCPMC10828925
OpenAlexW4391377502

What Socratic holds

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LicenceCC BY-NC
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 Socratic graph.