Acute on Chronic Liver FailureNCT06116305
Lactate Kinetics as a Predictor of Survival in ACLF With Septic Shock
An observational study of Acute on Chronic Liver Failure, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
Trial summary
Shock is a clinical state of tissue hypoxia. This hypoxia may be brought about by either decreased perfusion or the inability of the cell to extract oxygen in the presence of adequate perfusion. This causes cellular dysfunction. The most encountered form of shock seen in cirrhotics is septic shock. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute on Chronic Liver Failure
- How many people
- 100 participants
- Where
- 1 siteIndia
- Study dates
- 5 Nov 2023to 30 Aug 2024
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients of ACLF with septic shock who get admitted to our ICU with a diagnosis of septic shock in the age group 18 - 70 years.
Who may be able to join
- Patients of Acute on chronic liver failure with septic shock (APASL, Sepsis -3 definitions)
- Age 18-70yrs
- Informed Consent
Who cannot join
- Acute coronary syndrome, hemodynamically unstable arrhythmias
- CKD stage 5
- COPD with acute exacerbation
- Acute CVA or Seizures
- Extremely moribund patients
- Hepato-cellular carcinoma (HCC), intrahepatic or extrahepatic malignancy
- Pregnancy
- Diabetic ketoacidosis
Trial locations and contacts
1 site in 1 country.
India1 site
Institute of Liver & Biliary Sciences (ILBS)
New Delhi, National Capital Territory of Delhi, 110070
Dr Vishnu Girish, MD, 01146300000, vishnugirish@gmail.com
About this study
Official title: Lactate Kinetics as a Predictor of Survival in ACLF With Septic Shock: A Prospective Observational Study
Shock is a clinical state of tissue hypoxia. This hypoxia may be brought about by either decreased perfusion or the inability of the cell to extract oxygen in the presence of adequate perfusion. This causes cellular dysfunction. The most encountered form of shock seen in cirrhotics is septic shock. Septic shock has underlying cellular and metabolic abnormalities in addition to circulatory dysfunction. The circulatory dysfunction in sepsis is in the form of severe vasodilatation with high cardiac index. Cirrhosis is a state of hyperdynamic circulation. The mortality of septic shock in these group of patients is still higher. Sepsis-3 definition of septic shock describes it as a dysregulated immune response to an infection, leading to systemic inflammation, vasodilation, and organ impairment (3). Practically, to define septic shock it requires the lactate to be more than 2 mmol/L and there should be requirement of vasopressors after adequate fluid resuscitation.
Increased lactate levels can indicate tissue hypoxia, excessively rapid aerobic glycolysis, or reduced clearance. As lactate is a normal product of glucose and pyruvate metabolism, any increase in glucose metabolism and / or decrease in pyruvate metabolism will increase lactate generation. This was observed even in the presence of adequate tissue oxygenation. In sepsis, the inflammatory response appears to be associated with an increase in glycolysis and impaired pyruvate dehydrogenase activity. Thus, cytoplasmic pyruvate increases with greater lactate formation. The glycolytic enzyme complex lactate dehydrogenase (LDH) regenerates nicotinamide adenine dinucleotide (NAD) when pyruvate is reduced to lactate via a redox-coupled process in anaerobic glycolysis (Embden-Meyerhof pathway). Since lactate is overproduced and underutilised in tissue hypoxia due to poor mitochondrial oxidation, lactate has traditionally been used as a diagnostic marker for tissue hypoxia. However, up to 70% of the body's lactate elimination occurs in the liver
Read the detailed description
- We hypothesise that delta lactate at 6 hours would be a better predictor of survival in patients of ACLF with septic shock when compared to admission lactate
Aim and Objective -
- Aim: To study the impact of measurement of dynamic change of lactate on outcomes in ACLF patients with septic shock
- Primary objective: Delta arterial lactate at 6 hours (delta lactate) as a predictor of survival at 7 days in patients of ACLF with septic shock
Secondary objectives:
- To study the lactate kinetics and lactate clearance at different time points (0, 6, 12,24,48 and 72 hours)
- Impact of delta arterial lactate and lactate clearance at 6h on the length of hospital stay, days of ventilation, time taken for reversal of shock and 28-day mortality
- Impact of oxygenation, respiratory acidosis, metabolic acidosis, anion gap
- Effect of etiology of ACLF on lactate kinetics
- Study the impact of type of infection (MDRO) on lactate kinetics
- Study the impact of therapeutic interventions ( CRRT - impact of CRRT in a subgroup / Fluids/ Vasopressors) on lactate kinetics in ACLF patients with septic shock at day 7
- To develop a dynamic predictive model incorporating lactate kinetics to improve risk stratification and prediction of 28-day mortality.
Methodology:
Study population: Patients of ACLF with septic shock who get admitted to our ICU with a diagnosis of septic shock in the age group 18 - 70 years.
Study design: Prospective observational study Study period: 3 months
Study Location: Department of Hepatology, ILBS, New Delhi
Definitions Sepsis will be defined as a SOFA score more than 2 (or increase in SOFA score >2) in a patient with a suspected infection
Septic shock will be defined as Subset of patients with sepsis with hypotension (MAP <65) unresponsive to fluid boluses AND with lactate >2mmol/L despite adequate fluid resuscitation
Reversal of Shock will be defined as maintenance of MAP > 65mmHg after discontinuation of all vasopressors for 6 hours.
Lactic Acidosis
Hyperlactatemia
- Sample size with justification: No study has been done on lactate clearance in ACLF (APASL) with septic shock
- We have taken a sample size of 100 arbitrarily
- Intervention: Not applicable (Observational study)
- Monitoring and assessment:
- Statistical Analysis: Continuous data- Student's t test
- Nonparametric analysis- Mann Whitney test
- Survival outcome By Kaplan-Meier method curve.
- For all tests, p≤ 0.05 will be considered statistically significant.
- Analysis will be performed using SPSS .
- The analysis will be done with intention to treat and per protocol analysis if
- Adverse effects: N/A
- Stopping rule of study: N/A
- Conditions
- Acute on Chronic Liver Failure
- Being tested
- No intervention
- Medical subject headings
- Acute-On-Chronic Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No intervention
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants survived at day 7
Measured: 7 days
Secondary outcomes (26)
lactate clearance and delta lactate will be measured --> lactate clearance = (Initial lactate - current lactate) Initial lactate * 100, Delta lactate = Initial lactate - current lactate
Measured: 0 hours
lactate clearance and delta lactate will be measured --> lactate clearance = (Initial lactate - current lactate) Initial lactate * 100, Delta lactate = Initial lactate - current lactate
Measured: 6 hours
lactate clearance and delta lactate will be measured --> lactate clearance = (Initial lactate - current lactate) Initial lactate * 100, Delta lactate = Initial lactate - current lactate
Measured: 12 hours
lactate clearance and delta lactate will be measured --> lactate clearance = (Initial lactate - current lactate) Initial lactate * 100, Delta lactate = Initial lactate - current lactate
Measured: 24 hours
lactate clearance and delta lactate will be measured --> lactate clearance = (Initial lactate - current lactate) Initial lactate * 100, Delta lactate = Initial lactate - current lactate
Measured: 48 hours
lactate clearance and delta lactate will be measured --> lactate clearance = (Initial lactate - current lactate) Initial lactate * 100, Delta lactate = Initial lactate - current lactate
Measured: 72 hours
Impact of delta arterial lactate at 6 hours on length of hospital stay (measured in days).
Measured: 28 days
Impact of delta arterial lactate at 6 hours on need of invasive ventillation (Yes/no)
Measured: 7 days
Impact of delta arterial lactate at 6 hours on number of days of invasive ventillation (Measured in days)
Measured: 7 days
Impact of lactate clearance at 6 hours on length of hospital stay (measured in days).
Measured: 28 days
impact of lactate clearance at 6 hrs on need of invasive ventillation (Yes/no),
Measured: 7 days
impact of lactate clearance at 6 hrs on number of days of invasive ventillation (Measured in days)
Measured: 7 days
Length of hospital stay (measured in days).
Measured: 28 days
Need of ventilation
Measured: 28 days
Days of ventilation
Measured: 28 days
impact of oxygenation measured by PF ratio at 0H on delta lactate at 6 hours
Measured: 6 hours
Correlation between presence or absence of metabolic acidosis with delta lactate at 6 hours
Measured: 6 hours
Number of patients with effect of anion gap at 0H if metabolic acidosis is present on the delta lactate at 6 hours
Measured: 6 hours
Number of patients with effect of ejection fraction / cardiac outout on delta arterial lactate at 6 hours
Measured: 6 hours
To study the impact of presence or absence of multi drug resistant organism (in culture or PCR anallysis) on delta lactate at 6 hours
Measured: 7 days
The effect of need of renal replacement therapy (till day 7) on delta lactate at 6 hours
Measured: 7 days
The effect of number of days of continuous renal replacement therapy (till day7) on delta lactate at 6 hours
Measured: 7 days
The amount of fluid resuscitated and its effect on delta lactate at 6 hours
Measured: 7 days
Number of patients with number of patients with Noradrenaline requirement and effect on delta lactate at 6 hours
Measured: 7 days
To study the effect of lactate kinetics on 28 day mortality and to study the other factors affecting 28 day mortality
Measured: 28 days
Coerrelation between presence or absence of respiratory acidosis on the delta lactate at 6 hours
Measured: 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2023
- Study start5 Nov 2023 (estimated)
- Primary completion30 Aug 2024 (estimated)
- Study completion30 Aug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute on Chronic Liver FailureStudies of the same condition, open and under way.
- More trials run by Institute of Liver and Biliary Sciences, IndiaThe sponsor's other registered studies.
- 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
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06116305
- Sponsor's protocol ID
- ILBS-ACLF-13
- Status last verified
- Sep 2023
- First submitted
- 29 Sep 2023
- Last updated
- 3 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lactate Kinetics as a Predictor of Survival in ACLF With Septic Shock: A Prospective Observational Study
- ClinicalTrials.gov ID
- NCT06116305
- Acronym / sponsor ID
- ILBS-ACLF-13
- Conditions
- Acute on Chronic Liver Failure
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Study start
- 5 Nov 2023 (estimated)
- Primary completion
- 30 Aug 2024 (estimated)
- Study completion
- 30 Aug 2024 (estimated)
- First posted
- 3 Nov 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.
Shock is a clinical state of tissue hypoxia. This hypoxia may be brought about by either decreased perfusion or the inability of the cell to extract oxygen in the presence of adequate perfusion. This causes cellular dysfunction. The most encountered form of shock seen in cirrhotics is septic shock. Septic shock has underlying cellular and metabolic abnormalities in addition to circulatory dysfunction. The circulatory dysfunction in sepsis is in the form of severe vasodilatation with high cardiac index. Cirrhosis is a state of hyperdynamic circulation. The mortality of septic shock in these group of patients is still higher. Sepsis-3 definition of septic shock describes it as a dysregulated immune response to an infection, leading to systemic inflammation, vasodilation, and organ impairment (3). Practically, to define septic shock it requires the lactate to be more than 2 mmol/L and there should be requirement of vasopressors after adequate fluid resuscitation.
Increased lactate levels can indicate tissue hypoxia, excessively rapid aerobic glycolysis, or reduced clearance. As lactate is a normal product of glucose and pyruvate metabolism, any increase in glucose metabolism and / or decrease in pyruvate metabolism will increase lactate generation. This was observed even in the presence of adequate tissue oxygenation. In sepsis, the inflammatory response appears to be associated with an increase in glycolysis and impaired pyruvate dehydrogenase activity. Thus, cytoplasmic pyruvate increases with greater lactate formation. The glycolytic enzyme complex lactate dehydrogenase (LDH) regenerates nicotinamide adenine dinucleotide (NAD) when pyruvate is reduced to lactate via a redox-coupled process in anaerobic glycolysis (Embden-Meyerhof pathway). Since lactate is overproduced and underutilised in tissue hypoxia due to poor mitochondrial oxidation, lactate has traditionally been used as a diagnostic marker for tissue hypoxia. However, up to 70% of the body's lactate elimination occurs in the liver
Detailed description
- We hypothesise that delta lactate at 6 hours would be a better predictor of survival in patients of ACLF with septic shock when compared to admission lactate
Aim and Objective -
- Aim: To study the impact of measurement of dynamic change of lactate on outcomes in ACLF patients with septic shock
- Primary objective: Delta arterial lactate at 6 hours (delta lactate) as a predictor of survival at 7 days in patients of ACLF with septic shock
Secondary objectives:
- To study the lactate kinetics and lactate clearance at different time points (0, 6, 12,24,48 and 72 hours)
- Impact of delta arterial lactate and lactate clearance at 6h on the length of hospital stay, days of ventilation, time taken for reversal of shock and 28-day mortality
- Impact of oxygenation, respiratory acidosis, metabolic acidosis, anion gap
- Effect of etiology of ACLF on lactate kinetics
- Study the impact of type of infection (MDRO) on lactate kinetics
- Study the impact of therapeutic interventions ( CRRT - impact of CRRT in a subgroup / Fluids/ Vasopressors) on lactate kinetics in ACLF patients with septic shock at day 7
- To develop a dynamic predictive model incorporating lactate kinetics to improve risk stratification and prediction of 28-day mortality.
Methodology:
Study population: Patients of ACLF with septic shock who get admitted to our ICU with a diagnosis of septic shock in the age group 18 - 70 years.
Study design: Prospective observational study Study period: 3 months
Study Location: Department of Hepatology, ILBS, New Delhi
Definitions Sepsis will be defined as a SOFA score more than 2 (or increase in SOFA score >2) in a patient with a suspected infection
Septic shock will be defined as Subset of patients with sepsis with hypotension (MAP <65) unresponsive to fluid boluses AND with lactate >2mmol/L despite adequate fluid resuscitation
Reversal of Shock will be defined as maintenance of MAP > 65mmHg after discontinuation of all vasopressors for 6 hours.
Lactic Acidosis
Hyperlactatemia
- Sample size with justification: No study has been done on lactate clearance in ACLF (APASL) with septic shock
- We have taken a sample size of 100 arbitrarily
- Intervention: Not applicable (Observational study)
- Monitoring and assessment:
- Statistical Analysis: Continuous data- Student's t test
- Nonparametric analysis- Mann Whitney test
- Survival outcome By Kaplan-Meier method curve.
- For all tests, p≤ 0.05 will be considered statistically significant.
- Analysis will be performed using SPSS .
- The analysis will be done with intention to treat and per protocol analysis if
- Adverse effects: N/A
- Stopping rule of study: N/A
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients of ACLF with septic shock who get admitted to our ICU with a diagnosis of septic shock in the age group 18 - 70 years.
Key inclusion criteria (3 listed)
- Patients of Acute on chronic liver failure with septic shock (APASL, Sepsis -3 definitions)
- Age 18-70yrs
- Informed Consent
Key exclusion criteria (8 listed)
- Acute coronary syndrome, hemodynamically unstable arrhythmias
- CKD stage 5
- COPD with acute exacerbation
- Acute CVA or Seizures
- Extremely moribund patients
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 |
|---|---|---|
| No interventionNo intervention | Other | – |
Primary outcome
Number of participants survived at day 7
Time frame: 7 days
26 secondary outcomes
lactate clearance and delta lactate will be measured --> lactate clearance = (Initial lactate - current lactate) Initial lactate * 100, Delta lactate = Initial lactate - current lactate
Time frame: 0 hours
lactate clearance and delta lactate will be measured --> lactate clearance = (Initial lactate - current lactate) Initial lactate * 100, Delta lactate = Initial lactate - current lactate
Time frame: 6 hours
lactate clearance and delta lactate will be measured --> lactate clearance = (Initial lactate - current lactate) Initial lactate * 100, Delta lactate = Initial lactate - current lactate
Time frame: 12 hours
lactate clearance and delta lactate will be measured --> lactate clearance = (Initial lactate - current lactate) Initial lactate * 100, Delta lactate = Initial lactate - current lactate
Time frame: 24 hours
lactate clearance and delta lactate will be measured --> lactate clearance = (Initial lactate - current lactate) Initial lactate * 100, Delta lactate = Initial lactate - current lactate
Time frame: 48 hours
lactate clearance and delta lactate will be measured --> lactate clearance = (Initial lactate - current lactate) Initial lactate * 100, Delta lactate = Initial lactate - current lactate
Time frame: 72 hours
Impact of delta arterial lactate at 6 hours on length of hospital stay (measured in days).
Time frame: 28 days
Impact of delta arterial lactate at 6 hours on need of invasive ventillation (Yes/no)
Time frame: 7 days
Impact of delta arterial lactate at 6 hours on number of days of invasive ventillation (Measured in days)
Time frame: 7 days
Impact of lactate clearance at 6 hours on length of hospital stay (measured in days).
Time frame: 28 days
impact of lactate clearance at 6 hrs on need of invasive ventillation (Yes/no),
Time frame: 7 days
impact of lactate clearance at 6 hrs on number of days of invasive ventillation (Measured in days)
Time frame: 7 days
Length of hospital stay (measured in days).
Time frame: 28 days
Need of ventilation
Time frame: 28 days
Days of ventilation
Time frame: 28 days
impact of oxygenation measured by PF ratio at 0H on delta lactate at 6 hours
Time frame: 6 hours
Correlation between presence or absence of metabolic acidosis with delta lactate at 6 hours
Time frame: 6 hours
Number of patients with effect of anion gap at 0H if metabolic acidosis is present on the delta lactate at 6 hours
Time frame: 6 hours
Number of patients with effect of ejection fraction / cardiac outout on delta arterial lactate at 6 hours
Time frame: 6 hours
To study the impact of presence or absence of multi drug resistant organism (in culture or PCR anallysis) on delta lactate at 6 hours
Time frame: 7 days
The effect of need of renal replacement therapy (till day 7) on delta lactate at 6 hours
Time frame: 7 days
The effect of number of days of continuous renal replacement therapy (till day7) on delta lactate at 6 hours
Time frame: 7 days
The amount of fluid resuscitated and its effect on delta lactate at 6 hours
Time frame: 7 days
Number of patients with number of patients with Noradrenaline requirement and effect on delta lactate at 6 hours
Time frame: 7 days
To study the effect of lactate kinetics on 28 day mortality and to study the other factors affecting 28 day mortality
Time frame: 28 days
Coerrelation between presence or absence of respiratory acidosis on the delta lactate at 6 hours
Time frame: 6 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2023.
- Individual participant dataSharing planned: Undecided
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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.
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 Acute on Chronic Liver Failure, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
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 3 inclusion and 8 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 3 Nov 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 India. 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 Dr Vishnu Girish, MD (01146300000, vishnugirish@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants survived at day 7 (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Nov 2023.