Midregional proadrenomedullin safely reduces hospitalization in a low severity cohort with infections in the ED: a randomized controlled multi-centre interventional pilot study

Eur J Intern Med. 2021 Jun:88:104-113. doi: 10.1016/j.ejim.2021.03.041. Epub 2021 Apr 24.


Introduction: The midregional fragment of proadrenomedullin (MR-proADM) is known to provide accurate short-, mid- and long term prognostic information in the triage and multi-dimensional risk assessment of patients in the emergency department (ED). In two independent observational cohorts MR-proADM values identified low disease severity patients without risk of disease progression in the ED with no 28 days mortality that wouldn´t require hospitalization. In this interventional study we want to show that the combination of an MR-proADM algorithm with clinical assessment is able to identify low risk patients not requiring hospitalization to safely reduce the number of hospital admissions.

Methods: A randomized-controlled interventional multicenter study in 4 EDs in Spain. The study protocol was approved by Ethics Committees. Control arm patients received Standard Care. MR-proADM guided arm patients with low MR-proADM value (≤0.87 nmol/L) were treated as out-patients, with high MR-proADM value (>0.87 nmol/L) were hospitalized. The hospitalization rate was compared between the study arms.

Results: Two hundred patients with suspicion of infection were enrolled. In the MR-proADM guided arm the hospital admission rate in the intention-to-treat (ITT) population was 17% lower than in the control arm (40.6% vs. 57.6%, p=0.024) and 20% lower in the per protocol (PP) population (37.2% vs. 57.6%, p=0.009). No deaths of out-patients and no significant difference for the safety endpoints readmission and representation rates were observed. The readmission rate was only slightly higher in the MR-proADM guided arm compared to the control arm (PP population: at 14 days 9.3% vs. 7.1%, difference 2.1% (95% CI: -11.0% to 15.2%); and at 28 days 11.1% vs. 9.5%, difference 1.6% (95% CI: -12.2% to 15.4%)). The rate of 28 days representation was slightly lower in the MR-proADM guided arm compared to the control arm (20.4% vs. 26.2%, difference -5.8% (95% CI: -25.0% to 13.4%); PP population).

Conclusions: Implementing a MR-proADM algorithm optimizes ED workflows efficiently and sustainably. Hospitals can highly benefit from a reduced rate of hospitalizations by 20% using MR-proADM. The safety in the MR-proADM guided study arm was similar to the Standard Care arm.

Trial registration: ClinicalTrials.gov Identifier NCT03770533.

Keywords: Discharge; Disease Progression; Emergency Department; Hospitalization; Infection; MR-proADM; Readmission; Risk stratification.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin
  • Biomarkers
  • Emergency Service, Hospital*
  • Hospitalization*
  • Humans
  • Pilot Projects
  • Prognosis
  • Protein Precursors
  • Spain


  • Biomarkers
  • Protein Precursors
  • proadrenomedullin
  • Adrenomedullin

Associated data

  • ClinicalTrials.gov/NCT03770533