Septic ShockNCT07412366
Urea-to-Creatinine Ratio as a Marker of Metabolic Transition in Septic Shock: A Comparison With Indirect Calorimetry
An observational study of Septic Shock, run by Hospital Sao Domingos.
Trial summary
Urea-to-Creatinine Ratio as a Marker of Metabolic Transition in Septic Shock: A Comparison with Indirect Calorimetry. This study investigates whether the urea-to-creatinine ratio can serve as a simple marker of metabolic state in patients with septic shock. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2026to Oct 2027
- How long will I take part?
- 28 Days
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients with septic shock, defined according to Sepsis-3 criteria, admitted to a 53-bed medical-surgical intensive care unit between April 2026 and March 2027. Eligible patients will be required to have undergone invasive mechanical ventilation for at least three consecutive days and to have had energy expenditure measured by indirect calorimetry.
Inclusion Criteria: Adult patients with septic shock, defined according to Sepsis-3 criteria, admitted to a 53-bed medical-surgical intensive care unit between April 2026 and March 2027. Eligible patients will be required to have undergone invasive mechanical ventilation for at least three consecutive days -
Exclusion Criteria:Patients will be excluded if they had a serum creatinine level greater than 4.0 mg/dL at hospital admission, chronic kidney disease requiring dialysis, initiation of renal replacement therapy during ICU stay, or if they require an inspired oxygen fraction (FiO₂) greater than 70% on the fourth day of mechanical ventilation.
-
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Urea-to-Creatinine Ratio as a Marker of Metabolic Transition in Septic Shock: A Comparison with Indirect Calorimetry.
This study investigates whether the urea-to-creatinine ratio can serve as a simple marker of metabolic state in patients with septic shock. Septic shock is associated with hypermetabolism and severe protein catabolism, which worsen outcomes. Although indirect calorimetry is the gold standard for measuring energy expenditure and metabolic demand in critically ill patients, its availability in ICUs is limited.
Read more
The authors hypothesize that the urea-to-creatinine ratio reflects protein catabolism and correlates with energy expenditure measured by indirect calorimetry, making it a potential tool to identify the transition from the catabolic to the anabolic phase and to guide nutritional therapy. The primary objective is to assess the correlation between the urea-to-creatinine ratio and energy expenditure in septic shock patients. Secondary objectives include evaluating changes in systemic inflammation over time using C-reactive protein (CRP).
This is a prospective observational cohort study of adult patients with septic shock admitted to a medical-surgical ICU who require at least three days of mechanical ventilation and undergo indirect calorimetry. Energy expenditure will be measured at predefined intervals during the ICU stay, while urea, creatinine, and CRP levels will be collected regularly. Patients with severe renal dysfunction, renal replacement therapy, or high oxygen requirements will be excluded.
Data will be analyzed across three time periods during mechanical ventilation to examine trends in energy expenditure, urea-to-creatinine ratio, and inflammation. Demographic and clinical variables will also be collected. The study aims to determine whether changes in the urea-to-creatinine ratio mirror metabolic transitions detected by indirect calorimetry, potentially offering a practical alternative for metabolic monitoring in septic shock patients.
Read the detailed description
Urea-to-Creatinine Ratio as a Marker of Metabolic Transition in Septic Shock: A Comparison with Indirect Calorimetry
INTRODUCTION: Patients with septic shock develop profound metabolic alterations characterized by hypermetabolism and accelerated protein catabolism, leading to loss of lean body mass and worse clinical outcomes. Indirect calorimetry is the gold standard for assessing energy expenditure and metabolic demand in critically ill patients; however, it is not widely available in ICUs.
The urea-to-creatinine ratio has been proposed as a simple and readily available marker of protein catabolism. Nevertheless, its relationship with measured energy expenditure remains unclear.
HYPOTHESIS: The urea/creatinine ratio may be an efficient catabolism marker to guide nutritional therapy in critically ill patients. Evidence to confirm this hypothesis can be obtained by comparing the urea-to-creatinine ratio with indirect calorimetry, which is the gold standard for evaluating energy expenditure and metabolic demands in these patients.
OBJECTIVES: The primary objective of this study is to evaluate the correlation between the urea-to-creatinine ratio and energy expenditure measured by indirect calorimetry in patients with septic shock, in order to identify the transition from the catabolic to the anabolic phase. This transition is expected to be reflected by a reduction in the urea-to-creatinine ratio accompanied by a decrease in measured energy expenditure.
Secondary objectives include the analysis of inflammatory activity over time, as assessed by C-reactive protein (CRP) levels.
METHODS: This is a prospective observational cohort study including adult patients with septic shock, defined according to Sepsis-3 criteria, admitted to a 53-bed medical-surgical intensive care unit between April 2026 and March 2027. Eligible patients will be required to have undergone invasive mechanical ventilation for at least three consecutive days and to have had energy expenditure measured by indirect calorimetry.
Indirect calorimetry assessments will be performed on days 1, 4, 7, 11, 14, 17, and 20 after ICU admission. Patients will be excluded if they had a serum creatinine level greater than 4.0 mg/dL at hospital admission, chronic kidney disease requiring dialysis, initiation of renal replacement therapy during ICU stay, or if they require an inspired oxygen fraction (FiO₂) greater than 70% on the fourth day of mechanical ventilation.
Energy expenditure measurements will be obtained using the E-COVX module integrated into the Carescape B650 monitor (GE Healthcare, Helsinki, Finland). Urea and creatinine levels will be collected daily, and the urea-to-creatinine rati calculated accordingly. CRP levels will also be measured as an indicator of systemic inflammation.
For analysis, energy expenditure, urea-to-creatinine ratio, and CRP values will be grouped into three time periods based on days since initiation of mechanical ventilation: days 1-4, days 7-11, and days 14-20.
Demographic and clinical data to be collected include age, sex, Simplified Acute Physiology Score III (SAPS III), Sequential Organ Failure Assessment (SOFA) score at admission, admission category (medical or surgical), the sepsis focus and relevant comorbidities. Data will be collected prospectively using standardized case report forms.
Written informed consent will be obtained from patients or their legal representatives. The study protocol will be submitted for approval to the Research Ethics Committee of Hospital São Domingos
- Conditions
- Septic Shock
- Keywords
- urea-to-creatinine ratio, Indirect calorimetry, Septic shock, ICU, Catabolism
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Septic shock patients | Patients will be submmited to determinations os indirect calorimetry and urea-to-creatinine ratio on days 1, 4, 7, 11, 14, 17 and 20 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urea-to-creatinine ratio and energy expenditure measured by indirect calorimetry
To evaluate the correlation between the urea-to-creatinine ratio and energy expenditure measured by indirect calorimetry in patients with septic shock, in order to identify the transition from the catabolic to the anabolic phase. Urea and creatinine will be determined on days 1,4,7,11, 14,17 and 20. In the same period patients will be submmited to determination of energy expenditure by indirect calorimetry using the E-COVX module integrated into the Carescape B650 monitor (GE Healthcare, Helsinki, Finland).
Measured: 20 days
Secondary outcomes (1)
C-reactive protein (CRP)
Analysis of inflammatory activity over time, as assessed by C-reactive protein (CRP) levels.
Measured: 20 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2026
- Study start1 Apr 2026 (estimated)
- Primary completionMar 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
- Target duration
- 28 Days
Sponsor and investigators
- Lead sponsor
- Hospital Sao Domingos
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, José Raimundo Araujo de Azevedo, Hospital Sao Domingos
- Investigators
- JOSE AZEVEDO, MD, PhD, Principal investigator, Hospital Sao Domingos
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07412366
- Sponsor's protocol ID
- Study 01-2026
- Status last verified
- Jan 2026
- First submitted
- 9 Feb 2026
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Monk DN, Plank LD, Franch-Arcas G, Finn PJ, Streat SJ, Hill GL. Sequential changes in the metabolic response in critically injured patients during the first 25 days after blunt trauma. Ann Surg. 1996 Apr;223(4):395-405. doi: 10.1097/00000658-199604000-00008.
PubMed 8633918Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
PubMed 26903338Paulus MC, Melchers M, van Es A, Kouw IWK, van Zanten ARH. The urea-to-creatinine ratio as an emerging biomarker in critical care: a scoping review and meta-analysis. Crit Care. 2025 May 2;29(1):175. doi: 10.1186/s13054-025-05396-6.
PubMed 40317012Haines RW, Zolfaghari P, Wan Y, Pearse RM, Puthucheary Z, Prowle JR. Elevated urea-to-creatinine ratio provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma. Intensive Care Med. 2019 Dec;45(12):1718-1731. doi: 10.1007/s00134-019-05760-5. Epub 2019 Sep 17.
PubMed 31531715Niederer LE, Miller H, Haines KL, Molinger J, Whittle J, MacLeod DB, McClave SA, Wischmeyer PE. Prolonged progressive hypermetabolism during COVID-19 hospitalization undetected by common predictive energy equations. Clin Nutr ESPEN. 2021 Oct;45:341-350. doi: 10.1016/j.clnesp.2021.07.021. Epub 2021 Aug 3.
PubMed 34620338Long CL, Schaffel N, Geiger JW, Schiller WR, Blakemore WS. Metabolic response to injury and illness: estimation of energy and protein needs from indirect calorimetry and nitrogen balance. JPEN J Parenter Enteral Nutr. 1979 Nov-Dec;3(6):452-6. doi: 10.1177/014860717900300609.
PubMed 575168Israfilov E, Kir S. Comparison of Energy Expenditure in Mechanically Ventilated Septic Shock Patients in Acute and Recovery Periods via Indirect Calorimetry. JPEN J Parenter Enteral Nutr. 2021 Sep;45(7):1523-1531. doi: 10.1002/jpen.2063. Epub 2021 Feb 16.
PubMed 33314315
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Urea-to-Creatinine Ratio as a Marker of Metabolic Transition in Septic Shock: A Comparison With Indirect Calorimetry
- ClinicalTrials.gov ID
- NCT07412366
- Acronym / sponsor ID
- Study 01-2026
- Conditions
- Septic Shock
- Keywords
- urea-to-creatinine ratio, Indirect calorimetry, Septic shock, ICU, Catabolism
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Hospital Sao DomingosUniversity, hospital or other
- Study start
- 1 Apr 2026 (estimated)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 17 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Urea-to-Creatinine Ratio as a Marker of Metabolic Transition in Septic Shock: A Comparison with Indirect Calorimetry.
This study investigates whether the urea-to-creatinine ratio can serve as a simple marker of metabolic state in patients with septic shock. Septic shock is associated with hypermetabolism and severe protein catabolism, which worsen outcomes. Although indirect calorimetry is the gold standard for measuring energy expenditure and metabolic demand in critically ill patients, its availability in ICUs is limited.
The authors hypothesize that the urea-to-creatinine ratio reflects protein catabolism and correlates with energy expenditure measured by indirect calorimetry, making it a potential tool to identify the transition from the catabolic to the anabolic phase and to guide nutritional therapy. The primary objective is to assess the correlation between the urea-to-creatinine ratio and energy expenditure in septic shock patients. Secondary objectives include evaluating changes in systemic inflammation over time using C-reactive protein (CRP).
This is a prospective observational cohort study of adult patients with septic shock admitted to a medical-surgical ICU who require at least three days of mechanical ventilation and undergo indirect calorimetry. Energy expenditure will be measured at predefined intervals during the ICU stay, while urea, creatinine, and CRP levels will be collected regularly. Patients with severe renal dysfunction, renal replacement therapy, or high oxygen requirements will be excluded.
Data will be analyzed across three time periods during mechanical ventilation to examine trends in energy expenditure, urea-to-creatinine ratio, and inflammation. Demographic and clinical variables will also be collected. The study aims to determine whether changes in the urea-to-creatinine ratio mirror metabolic transitions detected by indirect calorimetry, potentially offering a practical alternative for metabolic monitoring in septic shock patients.
Detailed description
Urea-to-Creatinine Ratio as a Marker of Metabolic Transition in Septic Shock: A Comparison with Indirect Calorimetry
INTRODUCTION: Patients with septic shock develop profound metabolic alterations characterized by hypermetabolism and accelerated protein catabolism, leading to loss of lean body mass and worse clinical outcomes. Indirect calorimetry is the gold standard for assessing energy expenditure and metabolic demand in critically ill patients; however, it is not widely available in ICUs.
The urea-to-creatinine ratio has been proposed as a simple and readily available marker of protein catabolism. Nevertheless, its relationship with measured energy expenditure remains unclear.
HYPOTHESIS: The urea/creatinine ratio may be an efficient catabolism marker to guide nutritional therapy in critically ill patients. Evidence to confirm this hypothesis can be obtained by comparing the urea-to-creatinine ratio with indirect calorimetry, which is the gold standard for evaluating energy expenditure and metabolic demands in these patients.
OBJECTIVES: The primary objective of this study is to evaluate the correlation between the urea-to-creatinine ratio and energy expenditure measured by indirect calorimetry in patients with septic shock, in order to identify the transition from the catabolic to the anabolic phase. This transition is expected to be reflected by a reduction in the urea-to-creatinine ratio accompanied by a decrease in measured energy expenditure.
Secondary objectives include the analysis of inflammatory activity over time, as assessed by C-reactive protein (CRP) levels.
METHODS: This is a prospective observational cohort study including adult patients with septic shock, defined according to Sepsis-3 criteria, admitted to a 53-bed medical-surgical intensive care unit between April 2026 and March 2027. Eligible patients will be required to have undergone invasive mechanical ventilation for at least three consecutive days and to have had energy expenditure measured by indirect calorimetry.
Indirect calorimetry assessments will be performed on days 1, 4, 7, 11, 14, 17, and 20 after ICU admission. Patients will be excluded if they had a serum creatinine level greater than 4.0 mg/dL at hospital admission, chronic kidney disease requiring dialysis, initiation of renal replacement therapy during ICU stay, or if they require an inspired oxygen fraction (FiO₂) greater than 70% on the fourth day of mechanical ventilation.
Energy expenditure measurements will be obtained using the E-COVX module integrated into the Carescape B650 monitor (GE Healthcare, Helsinki, Finland). Urea and creatinine levels will be collected daily, and the urea-to-creatinine rati calculated accordingly. CRP levels will also be measured as an indicator of systemic inflammation.
For analysis, energy expenditure, urea-to-creatinine ratio, and CRP values will be grouped into three time periods based on days since initiation of mechanical ventilation: days 1-4, days 7-11, and days 14-20.
Demographic and clinical data to be collected include age, sex, Simplified Acute Physiology Score III (SAPS III), Sequential Organ Failure Assessment (SOFA) score at admission, admission category (medical or surgical), the sepsis focus and relevant comorbidities. Data will be collected prospectively using standardized case report forms.
Written informed consent will be obtained from patients or their legal representatives. The study protocol will be submitted for approval to the Research Ethics Committee of Hospital São Domingos
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 28 Days
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Septic shock patients | – | –Patients will be submmited to determinations os indirect calorimetry and urea-to-creatinine ratio on days 1, 4, 7, 11, 14, 17 and 20 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients with septic shock, defined according to Sepsis-3 criteria, admitted to a 53-bed medical-surgical intensive care unit between April 2026 and March 2027. Eligible patients will be required to have undergone invasive mechanical ventilation for at least three consecutive days and to have had energy expenditure measured by indirect calorimetry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Urea-to-creatinine ratio and energy expenditure measured by indirect calorimetry
Time frame: 20 days
To evaluate the correlation between the urea-to-creatinine ratio and energy expenditure measured by indirect calorimetry in patients with septic shock, in order to identify the transition from the catabolic to the anabolic phase. Urea and creatinine will be determined on days 1,4,7,11, 14,17 and 20. In the same period patients will be submmited to determination of energy expenditure by indirect calorimetry using the E-COVX module integrated into the Carescape B650 monitor (GE Healthcare, Helsinki, Finland).
1 secondary outcome
C-reactive protein (CRP)
Time frame: 20 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- Background: PubMed 8633918Monk DN, Plank LD, Franch-Arcas G, Finn PJ, Streat SJ, Hill GL. Sequential changes in the metabolic response in critically injured patients during the first 25 days after blunt trauma. Ann Surg. 1996 Apr;223(4):395-405. doi: 10.1097/00000658-199604000-00008.
- Background: PubMed 26903338Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
- Results publication: PubMed 40317012Paulus MC, Melchers M, van Es A, Kouw IWK, van Zanten ARH. The urea-to-creatinine ratio as an emerging biomarker in critical care: a scoping review and meta-analysis. Crit Care. 2025 May 2;29(1):175. doi: 10.1186/s13054-025-05396-6.
- Results publication: PubMed 31531715Haines RW, Zolfaghari P, Wan Y, Pearse RM, Puthucheary Z, Prowle JR. Elevated urea-to-creatinine ratio provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma. Intensive Care Med. 2019 Dec;45(12):1718-1731. doi: 10.1007/s00134-019-05760-5. Epub 2019 Sep 17.
- Results publication: PubMed 34620338Niederer LE, Miller H, Haines KL, Molinger J, Whittle J, MacLeod DB, McClave SA, Wischmeyer PE. Prolonged progressive hypermetabolism during COVID-19 hospitalization undetected by common predictive energy equations. Clin Nutr ESPEN. 2021 Oct;45:341-350. doi: 10.1016/j.clnesp.2021.07.021. Epub 2021 Aug 3.
- Results publication: PubMed 575168Long CL, Schaffel N, Geiger JW, Schiller WR, Blakemore WS. Metabolic response to injury and illness: estimation of energy and protein needs from indirect calorimetry and nitrogen balance. JPEN J Parenter Enteral Nutr. 1979 Nov-Dec;3(6):452-6. doi: 10.1177/014860717900300609.
- Results publication: PubMed 33314315Israfilov E, Kir S. Comparison of Energy Expenditure in Mechanically Ventilated Septic Shock Patients in Acute and Recovery Periods via Indirect Calorimetry. JPEN J Parenter Enteral Nutr. 2021 Sep;45(7):1523-1531. doi: 10.1002/jpen.2063. Epub 2021 Feb 16.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
JOSE AZEVEDO, MD, PhD principal investigator
Hospital Sao Domingos
Questions about this trial
What is this clinical trial studying?
An observational study of Septic Shock, run by Hospital Sao Domingos.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact JOSE AZEVEDO, MD, PhD (+55 98 991375595, jrazevedo47@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Urea-to-creatinine ratio and energy expenditure measured by indirect calorimetry (time frame: 20 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07412366, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.