Midodrine for the early liberation from vasopressor support in the ICU (LIBERATE): A Vanguard Randomized Clinical Trial
Notice bibliographique
Résumé
ABSTRACT Background Intravenous (IV) vasopressors are the mainstay of hemodynamic physiological support for critically ill patients. However, the role of oral vasopressors in the management of IV vasopressor-dependent shock remains unclear. The LIBERATE body of work aims to examine the role of midodrine as an IV vasopressor sparing agent for critically ill patients with IV vasopressor dependent shock. The objective of the LIBERATE internal randomized controlled trial was to evaluate the implementation of the LIBERATE protocol in a multi-centre randomized control trial setting. Methods We conducted a pilot multi-centre, concealed-allocation, parallel-group, blinded randomized controlled trial (RCT) evaluating the effect of midodrine 10mg q8h versus placebo on the duration of IV vasopressor-dependent shock in the intensive care unit (ICU) on the first 200 of planned sample size for the LIBERATE trial. The study was performed in 9 Alberta and Ontario medical centres between September 16, 2022 and January 22, 2025. We included patients aged 18 years or older admitted to the ICU receiving ongoing IV vasopressor support. Patients were randomly assigned 1:1 to enteral midodrine or an identical placebo and received the study treatment until 24 hours after discontinuation of their IV vasopressor therapy. The primary endpoints were study feasibility and included: recruitment rate (monthly enrollment per study site), screening and enrollment characteristics, protocol adherence, retention rate, data completeness, and safety (adverse event reporting), Secondary endpoints focused on aggregate patient-centered outcomes. Results There were 200 patients who fulfilled eligibility criteria and were enrolled in the trial. The mean age was 61.7 (SD 15.0), and 80 (40.1%) were female. The mean Acute Physiology and Health Evaluation (APACHE II) score at ICU admission was 23.7 (SD 7.6) and the mean Sequential Organ Failure Assessment (SOFA) score at the time of study enrollment was 10.1 (SD 2.9). Sepsis was the most common cause of shock in both groups. Average recruitment was 1.4 participants (range 0.3 to 3.0) per study site per month, protocol adherence was 84.5%, retention rate was 97.0%, and there were no reports of unblinding of treatment allocation by the study sites. Two adverse events were reported and resolved with no sequelae. Conclusion The LIBERATE internal randomized controlled trial is feasible and safe, supporting a larger trial to investigate the utility of midodrine in critically ill patients with IV vasopressor-dependent shock. Trial Registration Registered September 28, 2021. https://clinicaltrials.gov/study/ NCT05058612 Key messages regarding feasibility It was previously unknown if recruitment rates, protocol adherence and safety of midodrine would remain in effect across multiple centres This internal randomized controlled trial across 9 sites established sufficient feasibility outcomes with recruitment rates of 1.4 participants per site per month, protocol adherence of 84.5%, retention rates of 97.0%, data completeness of 96.0% and adverse event rate attributable to study medication of 0%. The results of this trial will be used to inform and proceed with the LIBERATE RCT.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,007 | 0,009 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,004 | 0,003 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,002 |
| Communication savante | 0,002 | 0,002 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,010 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».