NCT03966664

Brief Summary

Alterations of acid-base equilibrium are very common in critically ill patients and understanding their pathophysiology can be important to improve clinical treatment.

Trial Health

47
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
90

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Jun 2019

Geographic Reach
2 countries

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 27, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 29, 2019

Completed
5 days until next milestone

Study Start

First participant enrolled

June 3, 2019

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2021

Completed
Last Updated

June 4, 2019

Status Verified

June 1, 2019

Enrollment Period

2 years

First QC Date

May 27, 2019

Last Update Submit

June 3, 2019

Conditions

SepsisSeptic ShockCritical IllnessRespiratory AcidosisRespiratory AlkalosisAcid-Base Imbalance

Keywords

Acid-base equilibrium; pH; septic shock; critical illness

Outcome Measures

Primary Outcomes (1)

  • Effective dissociation constant of plasma weak acids (Ka) [dimensionless]

    Difference in plasma Ka between study groups.

    1 day

Secondary Outcomes (8)

  • Effective dissociation constant of whole blood weak acids (Ka) [dimensionless]

    1 day

  • Total concentration of plasma non-volatile buffers (Atot) [mmol/L]

    1 day

  • Total concentration of whole blood non-volatile buffers (Atot) [mmol/L]

    1 day

  • Non-carbonic buffer power of whole blood due to electrolyte shifts [milliequivalents/L]

    1 day

  • Non-carbonic buffer power of isolated plasma due to electrolyte shifts [milliequivalents/L]

    1 day

  • +3 more secondary outcomes

Study Arms (3)

Septic patients

Critically ill patients of both sexes admitted to the general ICU of the participating centers with the diagnosis of sepsis will be included.

Diagnostic Test: In vitro determination the dissociation constant (Ka) and total amount of non-volatile buffers (Atot) in isolated plasma.Diagnostic Test: In vitro determination the dissociation constant (Ka) and total amount of non-volatile buffers (Atot) in whole bloodDiagnostic Test: Biomolecular analysis of plasma proteins.

Healthy controls

Age and sex matched healthy volunteers.

Diagnostic Test: In vitro determination the dissociation constant (Ka) and total amount of non-volatile buffers (Atot) in isolated plasma.Diagnostic Test: In vitro determination the dissociation constant (Ka) and total amount of non-volatile buffers (Atot) in whole bloodDiagnostic Test: Biomolecular analysis of plasma proteins.

Non septic patients

Non-septic patients admitted to the general ICU of the participating centers after elective non-cardiac surgery.

Diagnostic Test: In vitro determination the dissociation constant (Ka) and total amount of non-volatile buffers (Atot) in isolated plasma.Diagnostic Test: In vitro determination the dissociation constant (Ka) and total amount of non-volatile buffers (Atot) in whole bloodDiagnostic Test: Biomolecular analysis of plasma proteins.

Interventions

In vitro determination the dissociation constant (Ka) and total amount of non-volatile buffers (Atot) in isolated plasma.DIAGNOSTIC_TEST

Collection of a venous blood sample, centrifugation in order to harvest isolated plasma and performance of in-vitro tonometry in order to assess Ka and Atot.

Healthy controlsNon septic patientsSeptic patients
In vitro determination the dissociation constant (Ka) and total amount of non-volatile buffers (Atot) in whole bloodDIAGNOSTIC_TEST

Collection of a venous blood sample and performance of in-vitro tonometry in order to assess Ka and Atot.

Healthy controlsNon septic patientsSeptic patients
Biomolecular analysis of plasma proteins.DIAGNOSTIC_TEST

Bidimensional electrophoresis, determination of oxidized albumin fraction, characterization of altered ligand binding properties of plasma albumin.

Healthy controlsNon septic patientsSeptic patients

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

1. Patients with sepsis or septic shock admitted to the ICU 2. Healthy volunteers recruited from ICU staff members and relatives 3. Non-septic patients admitted to the ICU after elective surgery

You may qualify if:

  • Diagnosis of Sepsis
  • Age \> 18 years
  • Informed or deferred informed consent

You may not qualify if:

  • Pregnancy
  • Bilirubin \> 4 mg/dL
  • Minor or major thalassemia
  • Transfusion of more than 4 Units of packed red blood cells and/or 1 L of plasma during the 24 hours prior to enrollment
  • Group 2: Healthy volunteers
  • informed consent
  • Age \> 18 years
  • Pregnancy
  • Group 3: Non-septic patients
  • Informed consent
  • Age \>18 years
  • Planned ICU admission after elective surgery
  • Diagnosis of sepsis
  • Pregnancy
  • Bilirubin \>4 mg/dL
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Third faculty of Medicine, Charles University of Prague

Prague, Czechia

RECRUITING

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Milan, 20122, Italy

RECRUITING

Related Publications (8)

  • Henderson LJ. THE REGULATION OF NEUTRALITY IN THE ANIMAL BODY. Science. 1913 Mar 14;37(950):389-95. doi: 10.1126/science.37.950.389. No abstract available.

    PMID: 17795147BACKGROUND

  • Lee SW, Hong YS, Park DW, Choi SH, Moon SW, Park JS, Kim JY, Baek KJ. Lactic acidosis not hyperlactatemia as a predictor of in hospital mortality in septic emergency patients. Emerg Med J. 2008 Oct;25(10):659-65. doi: 10.1136/emj.2007.055558.

    PMID: 18843064BACKGROUND

  • Fencl V, Leith DE. Stewart's quantitative acid-base chemistry: applications in biology and medicine. Respir Physiol. 1993 Jan;91(1):1-16. doi: 10.1016/0034-5687(93)90085-o.

    PMID: 8441866BACKGROUND

  • LEEUWEN AM. NET CATION EQUIVALENCY ('BASE BINDING POWER') OF THE PLASMA PROTEINS. Acta Med Scand. 1964;176:SUPPL 422: 1+. No abstract available.

    PMID: 14204741BACKGROUND

  • Figge J, Mydosh T, Fencl V. Serum proteins and acid-base equilibria: a follow-up. J Lab Clin Med. 1992 Nov;120(5):713-9.

    PMID: 1431499BACKGROUND

  • Stampfli HR, Misiaszek S, Lumsden JH, Carlson GP, Heigenhauser GJ. Weak acid-concentration Atot and dissociation constant Ka of plasma proteins in racehorses. Equine Vet J Suppl. 1999 Jul;(30):438-42.

    PMID: 10659296BACKGROUND

  • Staempfli HR, Constable PD. Experimental determination of net protein charge and A(tot) and K(a) of nonvolatile buffers in human plasma. J Appl Physiol (1985). 2003 Aug;95(2):620-30. doi: 10.1152/japplphysiol.00100.2003. Epub 2003 Mar 28.

    PMID: 12665532BACKGROUND

  • Langer T, Scotti E, Carlesso E, Protti A, Zani L, Chierichetti M, Caironi P, Gattinoni L. Electrolyte shifts across the artificial lung in patients on extracorporeal membrane oxygenation: interdependence between partial pressure of carbon dioxide and strong ion difference. J Crit Care. 2015 Feb;30(1):2-6. doi: 10.1016/j.jcrc.2014.09.013. Epub 2014 Sep 22.

    PMID: 25307980BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples in ethylenediaminetetraacetic acid for subsequent biomolecular analysis

MeSH Terms

Conditions

SepsisShock, SepticCritical IllnessAcidosis, RespiratoryAlkalosis, RespiratoryAcid-Base Imbalance

Condition Hierarchy (Ancestors)

InfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and SymptomsShockDisease AttributesRespiratory InsufficiencyRespiration DisordersRespiratory Tract DiseasesAcidosisMetabolic DiseasesNutritional and Metabolic DiseasesHyperventilationAlkalosis

Study Officials

  • Thomas Langer, MD

    Fondazione IRCCS Ca' Granda Hospital, Milano, Italy

    PRINCIPAL INVESTIGATOR

  • Antonio M Pesenti, MD

    Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

    STUDY CHAIR

  • Frantisek Duska, MD

    Third faculty of Medicine, Charles University, Prague

    PRINCIPAL INVESTIGATOR

  • Giacomo Grasselli, MD

    Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

    STUDY CHAIR

  • Paul Elbers, MD

    Amsterdam UMC, Department of Intensive Care Medicine

    STUDY CHAIR

Central Study Contacts

Thomas Langer, MD

CONTACT

0255033232thomas.langer@unimi.it

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 27, 2019

First Posted

May 29, 2019

Study Start

June 3, 2019

Primary Completion

June 1, 2021

Study Completion

June 1, 2021

Last Updated

June 4, 2019

Record last verified: 2019-06

Locations

CZ(1)IT(1)