Evidence map›Paper›PMID 25493978›Full record

Trial reportThe New England journal of medicine2014

A clinical trial of progesterone for severe traumatic brain injury.

Brett E Skolnick, Andrew I Maas, Raj K Narayan, Roland Gerritsen van der Hoop, Thomas MacAllister, John D Ward, Neta R Nelson, Nino Stocchetti, SYNAPSE Trial Investigators

3 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 236 papers, 14 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
236citing papers in PubMed, 14 pooled it
37.2field-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.

NCT01143064 phase3completednot on this map

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Investigate the Efficacy and Safety of Progesterone in Patients With Severe Traumatic Brain Injury

TypeinterventionalSponsorBHR Pharma, LLCRan2010 to 2014Enrolled1,195ConditionsBrain InjuriesArmsProgesterone, Lipid emulsion without progesterone
NCT06163833 phase2recruitingnot on this mapstarted 2023, after this paper: background citation

MATRIx: MesenchymAl Stromal Cells for Traumatic bRain Injury

TypeinterventionalSponsorFondazione IRCCS San Gerardo dei TintoriRan2023 to 2026Enrolled78ConditionsTraumatic Brain Injury With Loss of ConsciousnessArmsMesenchymal stromal cell low dosage-80*10^6 cells, Mesenchymal stromal cell low dosage-160*10^6 cells, Placebo-storage solution
NCT06429657 phase4suspendednot on this mapstarted 2024, after this paper: background citation

Ketamine for Sedation in Severe Traumatic Brain Injury

TypeinterventionalSponsorHenry M. Jackson Foundation for the Advancement of Military MedicineRan2024 to 2027Enrolled50ConditionsSevere Traumatic Brain Injury, Intracranial Hypertension, Intracranial Hemorrhage, HypertensiveArmsKetamine with propofol, Standard of Care propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam
3 · Its place in the literature

Who cites it

236 citing papers in PubMed, 14 syntheses or guidelines pooled it, 492 citations in OpenAlex.

  1. Pooled it
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  10. Guideline
  11. Guideline
  12. Progesterone for acute traumatic brain injury.The Cochrane database of systematic reviews · 2016
    Pooled it
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  15. Trial
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  17. Presenting Characteristics Associated With Outcome in Children With Severe Traumatic Brain Injury: A Secondary Analysis From a Randomized, Controlled Trial of Therapeutic Hypothermia.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2018
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176 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Brett E SkolnickFrom the Department of Neurosurgery, Cushing Neuroscience Institute, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY (B.E.S., R.K.N.); the Department of Neurosurgery, University Hospital Antwerp and University of Antwerp, Edegem, Belgium (A.I.M.); BHR Pharma, Herndon (R.G.H., T.M., N.R.N.), and the Department of Neurosurgery, Virginia Commonwealth University, Richmond (J.D.W.) - both in Virginia; and the Department of Physiopathology and Transplantation, Milan University and Neuro Intensive Care Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Cà Granda Ospedale Maggiore Policlinico, Milan (N.S.).
Andrew I Maas
Raj K Narayan
Roland Gerritsen van der Hoop
Thomas MacAllister
John D Ward
Neta R Nelson
Nino Stocchetti
SYNAPSE Trial Investigators
Antwerp University Hospital · BEFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico · ITVirginia Commonwealth University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundProgesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. We investigated the efficacy and safety of progesterone in a large, prospective, phase 3 randomized clinical trial.

methodsWe conducted a multinational placebo-controlled trial, in which 1195 patients, 16 to 70 years of age, with severe TBI (Glasgow Coma Scale score, ≤8 [on a scale of 3 to 15, with lower scores indicating a reduced level of consciousness] and at least one reactive pupil) were randomly assigned to receive progesterone or placebo. Dosing began within 8 hours after injury and continued for 120 hours. The primary efficacy end point was the Glasgow Outcome Scale score at 6 months after the injury.

resultsProportional-odds analysis with covariate adjustment showed no treatment effect of progesterone as compared with placebo (odds ratio, 0.96; confidence interval, 0.77 to 1.18). The proportion of patients with a favorable outcome on the Glasgow Outcome Scale (good recovery or moderate disability) was 50.4% with progesterone, as compared with 50.5% with placebo. Mortality was similar in the two groups. No relevant safety differences were noted between progesterone and placebo.

conclusionsPrimary and secondary efficacy analyses showed no clinical benefit of progesterone in patients with severe TBI. These data stand in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials. (Funded by BHR Pharma; SYNAPSE ClinicalTrials.gov number, NCT01143064.).

Indexed as

AdolescentAdultAgedBrain InjuriesDouble-Blind MethodDrug Administration ScheduleFemaleGlasgow Coma ScaleGlasgow Outcome ScaleHumansInfusions, IntravenousIntention to Treat AnalysisMaleMiddle AgedOdds RatioProgesteroneProgesterone

Identifiers

PMID25493978
OpenAlexW2046037876

What OpenQuestion holds

Textmetadata
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.