Liver DysfunctionNCT05999331
Elevated Initial APRI Value Was Associated With SALD
An observational study of Liver Dysfunction and Sepsis-associated Liver Dysfunction, run by Chinese Medical Association at 1 site in China.
Trial summary
Sepsis, characterized by severe organ dysfunction related to a dysregulated immune response to infection, is often life-threatening in clinical settings. Sepsis can progress to multiple organ dysfunction syndrome (MODS), causing a great risk of mortality. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Liver Dysfunction, Sepsis-associated Liver Dysfunction
- What is being tested?
- initial aspartate aminotransferase (AST) to platelet (PLT) ratio index
- How many people
- 160 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2019to 30 Sep 2023
- How long will I take part?
- 30 Days
- Phase
- Observational
- Are there results?
- None posted in the registry
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 to 90 years
- All sexes
- Adult, Older adult
Study population: Briefly, patients with confirmed or suspected foci of infectious and a concurrent SOFA≥2 were diagnosed with sepsis. SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL.
Who may be able to join
- adult sepsis patients (≥18 years)
Who cannot join
- all types of chronic liver disease;
- viral hepatitis;
- primary acute cholangiopathies;
- cholecystitis;
- hepatic infarction;
- liver necrosis;
Show all 9Show fewer
- liver trauma;
- length of ICU stay < 24 hours;
- Patients without simultaneous AST and PLT data in the first 24 hours after ICU admission.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Institute of General Surgery of Jinling Hospital
Nanjing, Jiangsu, 210002
Wenkui Yu, Ph.D., 13701582986, yudrnj@163.com
About this study
Official title: Elevated Initial APRI Value Was Associated With the Development of Sepsis-associated Liver Dysfunction in Adult Patients With Sepsis
Sepsis, characterized by severe organ dysfunction related to a dysregulated immune response to infection, is often life-threatening in clinical settings. Sepsis can progress to multiple organ dysfunction syndrome (MODS), causing a great risk of mortality. As a vital immune and metabolic organ, liver often suffers damage in this process and often associated with severe adverse consequences. Compared to general sepsis population, sepsis-associated liver dysfunction (SALD) has a higher mortality, up to 68.6%.
The aspartate aminotransferase (AST) to platelet (PLT) ratio index (APRI), which can be calculated from conventional laboratory indicators, has long been used in the evaluation of liver damage and fibrosis in patients with hepatitis and nonalcoholic fatty liver disease. AST is a sensitive indicator of early liver function impairment. Additionally, PLT also plays a crucial role in sepsis-induced MODS through regulating inflammation, maintaining tissue integrity, and defending against infection. Study found that APRI was a good predictor of SALD occurrence in pediatric patients with sepsis. Furthermore, APRI has also been used to predict the prognostic in septic patients with no history of chronic liver disease.
We conducted a retrospective study based on data from the Medical Information Mart for Intensive Care IV version 2.2 (MIMIC-IV, v2.2) and our own hospital to explore the potential association of APRI with the occurrence of SALD in adult patients with sepsis. Furthermore, we also evaluated the performance of APRI in hypoxic hepatitis and sepsis induced cholestasis (SIC), which are two subtypes of SALD.
Read the detailed description
We included adult sepsis patients (≥18 years) as study participants, but only those who had data available for their first hospitalization and first ICU admission were enrolled in our study, if they had multiple admission records in the database. Exclusion criteria include: 1) all types of chronic liver disease; 2) viral hepatitis; 3) primary acute cholangiopathies; 4) cholecystitis; 5) hepatic infarction; 6) liver necrosis; 7) liver trauma; 8) length of ICU stay < 24 hours. Patients without simultaneous AST and PLT data in the first 24 hours after ICU admission were also excluded.
The following indicators were extracted directly or derived from the database(MIMIC IV): age; weight; gender; comorbidity, including hypertension, old myocardial infarct, chronic heart failure, cerebrovascular disease, chronic pulmonary disease, chronic renal disease and diabetes; infection site, including blood, lung, skin and soft tissue, abdominal cavity and urinary tract; disease severity scores within the first day of ICU admission, including Acute Physiology Score III (APS III), Sequential Organ Failure Assessment (SOFA), Logistic Organ Dysfunction Score (LODS), Oxford Acute Severity of illness Score (OASIS) and Simplified Acute Physiology Score II (SAPS II); mean vital signs in first 24h, including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), respiratory rate (RR), temperature and pulse oxygen saturation (SPO2); treatment received within the first day of ICU admission, including invasive ventilation, vasopressor therapy, renal replacement therapy and parenteral nutrition (PN) support; initial laboratory parameters, including white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell (RBC), red blood cell distribution width (RDW), platelet, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), albumin, blood urea nitrogen (BUN), creatinine, bicarbonate, anionic gap, sodium, potassium, chloride, total calcium, glucose, prothrombin time (PT), partial prothrombine time (APTT), international normalized ratio (INR) and APRI; clinical outcome measures, including intensive care unit (ICU) length of stay (LOS), hospital LOS, ICU mortality, in-hospital mortality, and 30-day mortality.
The disease severity scores, including APS III, SOFA, LODS, OASIS, SAPS II, are calculated using the SQL code provided by Johnson et al. APRI is calculated by (AST(IU/L)/ upper limits of normal)/PLT(k/uL)×100. Sepsis is diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Briefly, patients with confirmed or suspected foci of infectious and a concurrent SOFA≥2. SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. SALD is further divided into hypoxic hepatitis and sepsis induced cholestasis (SIC), based on the presence or absence of elevated TBIL. Hypoxic hepatitis is diagnosed when elevated transaminase (>800 IU/L) is present only; and SIC is diagnosed when TBIL is elevated (≥2.0 mg/dL). Following the exclusion of ineligible patients, the data underwent a thorough examination, and extreme and erroneous values that failed logical checks were removed. Variables with missing data exceeding 30% of the sample size were excluded. For the remaining variables with missing values, the mean imputation method was applied to address them.
We first used the MIMIC IV database to assess the correlation between APRI and the occurrence of SALD using association analysis. We then validated these results using our own data.
- Being tested
- initial aspartate aminotransferase (AST) to platelet (PLT) ratio index
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
initial aspartate aminotransferase (AST) to platelet (PLT) ratio indexOther
All eligible patients were given antibiotics therapy, actively control infection source, as well as other supportive therapy to maintain organ function.
| Study group | Role | What they receive |
|---|---|---|
| Non-SALD group | SALD did not occur in adult patients with sepsis during ICU stay.SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. Receives: Other: initial aspartate aminotransferase (AST) to platelet (PLT) ratio index | |
| SALD group | SALD was occured in adult patients with sepsis during ICU stay.SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. SALD is further divided into hypoxic hepatitis and sepsis induced cholestasis (SIC), based on the presence or absence of elevated TBIL. Hypoxic hepatitis is diagnosed when elevated transaminase (>800 IU/L) is present only; and SIC is diagnosed when TBIL is elevated (≥2.0 mg/dL). Receives: Other: initial aspartate aminotransferase (AST) to platelet (PLT) ratio index |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of SALD
Whether SALD occurs
Measured: 30 days after ICU admission
Secondary outcomes (1)
mortality
Death at 30 days after ICU
Measured: 30 days after ICU admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2023
- Study start1 Jan 2019
- Primary completion30 Sep 2023 (estimated)
- Study completion30 Sep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Liver DysfunctionStudies 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
- 160 participants (estimated)
- Target duration
- 30 Days
Sponsor and investigators
- Lead sponsor
- Chinese Medical Association
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Wenkui Yu, professor, Study chair, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05999331
- Sponsor's protocol ID
- 2023-06-03
- Status last verified
- Jun 2023
- First submitted
- 11 Aug 2023
- Last updated
- 21 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The research is not over yet
Publications
Dou J, Zhou Y, Cui Y, Chen M, Wang C, Zhang Y. AST-to-Platelet Ratio Index as Potential Early-Warning Biomarker for Sepsis-Associated Liver Injury in Children: A Database Study. Front Pediatr. 2019 Aug 21;7:331. doi: 10.3389/fped.2019.00331. eCollection 2019.
PubMed 31497584Zhu X, Hu X, Qin X, Pan J, Zhou W. An elevated Fibrosis-4 score is associated with poor clinical outcomes in patients with sepsis: an observational cohort study. Pol Arch Intern Med. 2020 Dec 22;130(12):1064-1073. doi: 10.20452/pamw.15699. Epub 2020 Dec 4.
PubMed 33274619
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Elevated Initial APRI Value Was Associated With the Development of Sepsis-associated Liver Dysfunction in Adult Patients With Sepsis
- ClinicalTrials.gov ID
- NCT05999331
- Acronym / sponsor ID
- 2023-06-03
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Chinese Medical AssociationResearch network
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 30 Sep 2023 (estimated)
- Study completion
- 30 Sep 2023 (estimated)
- First posted
- 21 Aug 2023 (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.
Sepsis, characterized by severe organ dysfunction related to a dysregulated immune response to infection, is often life-threatening in clinical settings. Sepsis can progress to multiple organ dysfunction syndrome (MODS), causing a great risk of mortality. As a vital immune and metabolic organ, liver often suffers damage in this process and often associated with severe adverse consequences. Compared to general sepsis population, sepsis-associated liver dysfunction (SALD) has a higher mortality, up to 68.6%.
The aspartate aminotransferase (AST) to platelet (PLT) ratio index (APRI), which can be calculated from conventional laboratory indicators, has long been used in the evaluation of liver damage and fibrosis in patients with hepatitis and nonalcoholic fatty liver disease. AST is a sensitive indicator of early liver function impairment. Additionally, PLT also plays a crucial role in sepsis-induced MODS through regulating inflammation, maintaining tissue integrity, and defending against infection. Study found that APRI was a good predictor of SALD occurrence in pediatric patients with sepsis. Furthermore, APRI has also been used to predict the prognostic in septic patients with no history of chronic liver disease.
We conducted a retrospective study based on data from the Medical Information Mart for Intensive Care IV version 2.2 (MIMIC-IV, v2.2) and our own hospital to explore the potential association of APRI with the occurrence of SALD in adult patients with sepsis. Furthermore, we also evaluated the performance of APRI in hypoxic hepatitis and sepsis induced cholestasis (SIC), which are two subtypes of SALD.
Detailed description
We included adult sepsis patients (≥18 years) as study participants, but only those who had data available for their first hospitalization and first ICU admission were enrolled in our study, if they had multiple admission records in the database. Exclusion criteria include: 1) all types of chronic liver disease; 2) viral hepatitis; 3) primary acute cholangiopathies; 4) cholecystitis; 5) hepatic infarction; 6) liver necrosis; 7) liver trauma; 8) length of ICU stay < 24 hours. Patients without simultaneous AST and PLT data in the first 24 hours after ICU admission were also excluded.
The following indicators were extracted directly or derived from the database(MIMIC IV): age; weight; gender; comorbidity, including hypertension, old myocardial infarct, chronic heart failure, cerebrovascular disease, chronic pulmonary disease, chronic renal disease and diabetes; infection site, including blood, lung, skin and soft tissue, abdominal cavity and urinary tract; disease severity scores within the first day of ICU admission, including Acute Physiology Score III (APS III), Sequential Organ Failure Assessment (SOFA), Logistic Organ Dysfunction Score (LODS), Oxford Acute Severity of illness Score (OASIS) and Simplified Acute Physiology Score II (SAPS II); mean vital signs in first 24h, including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), respiratory rate (RR), temperature and pulse oxygen saturation (SPO2); treatment received within the first day of ICU admission, including invasive ventilation, vasopressor therapy, renal replacement therapy and parenteral nutrition (PN) support; initial laboratory parameters, including white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell (RBC), red blood cell distribution width (RDW), platelet, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), albumin, blood urea nitrogen (BUN), creatinine, bicarbonate, anionic gap, sodium, potassium, chloride, total calcium, glucose, prothrombin time (PT), partial prothrombine time (APTT), international normalized ratio (INR) and APRI; clinical outcome measures, including intensive care unit (ICU) length of stay (LOS), hospital LOS, ICU mortality, in-hospital mortality, and 30-day mortality.
The disease severity scores, including APS III, SOFA, LODS, OASIS, SAPS II, are calculated using the SQL code provided by Johnson et al. APRI is calculated by (AST(IU/L)/ upper limits of normal)/PLT(k/uL)×100. Sepsis is diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Briefly, patients with confirmed or suspected foci of infectious and a concurrent SOFA≥2. SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. SALD is further divided into hypoxic hepatitis and sepsis induced cholestasis (SIC), based on the presence or absence of elevated TBIL. Hypoxic hepatitis is diagnosed when elevated transaminase (>800 IU/L) is present only; and SIC is diagnosed when TBIL is elevated (≥2.0 mg/dL). Following the exclusion of ineligible patients, the data underwent a thorough examination, and extreme and erroneous values that failed logical checks were removed. Variables with missing data exceeding 30% of the sample size were excluded. For the remaining variables with missing values, the mean imputation method was applied to address them.
We first used the MIMIC IV database to assess the correlation between APRI and the occurrence of SALD using association analysis. We then validated these results using our own data.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 30 Days
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-SALD group | – | Other: initial aspartate aminotransferase (AST) to platelet (PLT) ratio indexSALD did not occur in adult patients with sepsis during ICU stay.SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. |
| SALD group | – | Other: initial aspartate aminotransferase (AST) to platelet (PLT) ratio indexSALD was occured in adult patients with sepsis during ICU stay.SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. SALD is further divided into hypoxic hepatitis and sepsis induced cholestasis (SIC), based on the presence or absence of elevated TBIL. Hypoxic hepatitis is diagnosed when elevated transaminase (>800 IU/L) is present only; and SIC is diagnosed when TBIL is elevated (≥2.0 mg/dL). |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Briefly, patients with confirmed or suspected foci of infectious and a concurrent SOFA≥2 were diagnosed with sepsis. SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL.
Key inclusion criteria (1 listed)
- adult sepsis patients (≥18 years)
Key exclusion criteria (9 listed)
- all types of chronic liver disease;
- viral hepatitis;
- primary acute cholangiopathies;
- cholecystitis;
- hepatic infarction;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| initial aspartate aminotransferase (AST) to platelet (PLT) ratio indexAll eligible patients were given antibiotics therapy, actively control infection source, as well as other supportive therapy to maintain organ function. | Other | Non-SALD group, SALD group |
Primary outcome
Occurrence of SALD
Time frame: 30 days after ICU admission
Whether SALD occurs
1 secondary outcome
mortality
Time frame: 30 days after ICU admission
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2023.
- Background: PubMed 31497584Dou J, Zhou Y, Cui Y, Chen M, Wang C, Zhang Y. AST-to-Platelet Ratio Index as Potential Early-Warning Biomarker for Sepsis-Associated Liver Injury in Children: A Database Study. Front Pediatr. 2019 Aug 21;7:331. doi: 10.3389/fped.2019.00331. eCollection 2019.
- Background: PubMed 33274619Zhu X, Hu X, Qin X, Pan J, Zhou W. An elevated Fibrosis-4 score is associated with poor clinical outcomes in patients with sepsis: an observational cohort study. Pol Arch Intern Med. 2020 Dec 22;130(12):1064-1073. doi: 10.20452/pamw.15699. Epub 2020 Dec 4.
- Individual participant dataSharing planned: No. The research is not over yet
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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. This study is not recruiting at the moment.
Wenkui Yu, professor study chair
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Dysfunction and Sepsis-associated Liver Dysfunction, run by Chinese Medical Association at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. 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: status not confirmed, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Beiyuan Zhang, M.S. (15005170137, 1083537599@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of SALD (time frame: 30 days after ICU admission). 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 NCT05999331, which also lists 2 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 21 Aug 2023.