Evidence map›Paper›PMID 28877748›Full record

Trial reportCritical care (London, England)2017

A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome.

Akram Khan, Cody Benthin, Brian Zeno, Timothy E Albertson, John Boyd, Jason D Christie, Richard Hall, Germain Poirier, Juan J Ronco, Mark Tidswell and 8 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 Critical care (London, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01597635 (A Two Part Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2586881 in Patients With Acute Lung Injury), which is not on this map. Cited by 397 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
397citing papers in PubMed, 3 pooled it
57.3field-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.

NCT01597635 phase2completednot on this map

A Two Part Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2586881 in Patients With Acute Lung Injury

TypeinterventionalSponsorGlaxoSmithKlineRan2012 to 2014Enrolled44ConditionsLung Injury, AcuteArmsDose 1 GSK2586881, Dose 2 GSK2586881, Dose 3 GSK2586881, Dose 4 GSK2586881, Placebo (saline)
3 · Its place in the literature

Who cites it

397 citing papers in PubMed, 3 syntheses or guidelines pooled it, 626 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 11 institutions in 3 countries.

Akram KhanDiv. of Pulmonary & Critical Care Medicine, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
Cody BenthinDiv. of Pulmonary & Critical Care Medicine, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
Brian ZenoRiverside Methodist Hospital, Columbus, OH, USA.
Timothy E AlbertsonSchool of Medicine, University of California, Davis, Sacramento, CA, USA.
John BoydSt. Paul's Hospital, Vancouver, BC, Canada.
Jason D ChristieDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Richard HallNova Scotia Health Authority and Dalhousie University, Halifax, NS, Canada.
Germain PoirierCharles LeMoyne Hospital, Sherbrooke University, Greenfield Park, QC, Canada.
Juan J RoncoCritical Care Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
Mark TidswellDivision of Pulmonary and Critical Care, Department of Medicine, Baystate Medical Center, Springfield, MA, USA.
Kelly HardesGlaxoSmithKline R&D, Stockley Park, UK.
William M PowleyGlaxoSmithKline R&D, Stevenage, UK.
Tracey J WrightGlaxoSmithKline R&D, Stevenage, UK.
Sarah K SiedererGlaxoSmithKline R&D, Stevenage, UK.
David A FairmanGlaxoSmithKline R&D, Stevenage, UK.
David A LipsonDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Andrew I BayliffeGlaxoSmithKline R&D, Stevenage, UK.
Aili L LazaarDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. aili.l.lazaar@gsk.com.
GlaxoSmithKline (United Kingdom) · GBGlaxoSmithKline (United States) · USOregon Health & Science University · USBaystate Medical Center · USHôpital Charles-Le Moyne · CANova Scotia Health Authority · CARiverside Methodist Hospital · USSt. Paul's Hospital · CAUniversity of California, Davis · USUniversity of Pennsylvania · USVancouver General Hospital · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRenin-angiotensin system (RAS) signaling and angiotensin-converting enzyme 2 (ACE2) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We postulated that repleting ACE2 using GSK2586881, a recombinant form of human angiotensin-converting enzyme 2 (rhACE2), could attenuate acute lung injury.

methodsWe conducted a two-part phase II trial comprising an open-label intrapatient dose escalation and a randomized, double-blind, placebo-controlled phase in ten intensive care units in North America. Patients were between the ages of 18 and 80 years, had an American-European Consensus Criteria consensus diagnosis of ARDS, and had been mechanically ventilated for less than 72 h. In part A, open-label GSK2586881 was administered at doses from 0.1 mg/kg to 0.8 mg/kg to assess safety, pharmacokinetics, and pharmacodynamics. Following review of data from part A, a randomized, double-blind, placebo-controlled investigation of twice-daily doses of GSK2586881 (0.4 mg/kg) for 3 days was conducted (part B). Biomarkers, physiological assessments, and clinical endpoints were collected over the dosing period and during follow-up.

resultsDose escalation in part A was well-tolerated without clinically significant hemodynamic changes. Part B was terminated after 39 of the planned 60 patients following a planned futility analysis. Angiotensin II levels decreased rapidly following infusion of GSK2586881, whereas angiotensin-(1-7) and angiotensin-(1-5) levels increased and remained elevated for 48 h. Surfactant protein D concentrations were increased, whereas there was a trend for a decrease in interleukin-6 concentrations in rhACE2-treated subjects compared with placebo. No significant differences were noted in ratio of partial pressure of arterial oxygen to fraction of inspired oxygen, oxygenation index, or Sequential Organ Failure Assessment score.

conclusionsGSK2586881 was well-tolerated in patients with ARDS, and the rapid modulation of RAS peptides suggests target engagement, although the study was not powered to detect changes in acute physiology or clinical outcomes.

trial registrationClinicalTrials.gov, NCT01597635 . Registered on 26 January 2012.

Indexed as

AdultAgedAngiotensin-Converting Enzyme 2Blood Gas AnalysisDouble-Blind MethodFemaleHumansIntensive Care UnitsMaleMiddle AgedNorth AmericaPeptidyl-Dipeptidase APilot ProjectsPlacebosRespiratory Distress SyndromeACE2 protein, humanAngiotensin-Converting Enzyme 2Peptidyl-Dipeptidase APlacebosAcute lung injuryAcute respiratory failureAdultAngiotensin-converting enzyme 2HumansInterleukin-6Renin-angiotensin systemRespiratory distress syndrome

Identifiers

PMID28877748
PMCPMC5588692
OpenAlexW2753321278

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.