- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06116305
Lactate Kinetics as a Predictor of Survival in ACLF With Septic Shock
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Dr Vishnu Girish, MD
- Phone Number: 01146300000
- Email: vishnugirish@gmail.com
Study Locations
-
-
Delhi
-
New Delhi, Delhi, India, 110070
- Institute of Liver & Biliary Sciences (ILBS)
-
Contact:
- Dr Vishnu Girish, MD
- Phone Number: 01146300000
- Email: vishnugirish@gmail.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Patients of Acute on chronic liver failure with septic shock (APASL, Sepsis -3 definitions)
- Age 18-70yrs
- Informed Consent
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of participants survived at day 7
Time Frame: 7 days
|
7 days
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
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
|
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
|
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
|
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
|
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
|
72 hours
|
Impact of delta arterial lactate at 6 hours on length of hospital stay (measured in days).
Time Frame: 28 days
|
28 days
|
Impact of delta arterial lactate at 6 hours on need of invasive ventillation (Yes/no)
Time Frame: 7 days
|
7 days
|
Impact of delta arterial lactate at 6 hours on number of days of invasive ventillation (Measured in days)
Time Frame: 7 days
|
7 days
|
Impact of lactate clearance at 6 hours on length of hospital stay (measured in days).
Time Frame: 28 days
|
28 days
|
impact of lactate clearance at 6 hrs on need of invasive ventillation (Yes/no),
Time Frame: 7 days
|
7 days
|
impact of lactate clearance at 6 hrs on number of days of invasive ventillation (Measured in days)
Time Frame: 7 days
|
7 days
|
Length of hospital stay (measured in days).
Time Frame: 28 days
|
28 days
|
Need of ventilation
Time Frame: 28 days
|
28 days
|
Days of ventilation
Time Frame: 28 days
|
28 days
|
impact of oxygenation measured by PF ratio at 0H on delta lactate at 6 hours
Time Frame: 6 hours
|
6 hours
|
Correlation between presence or absence of metabolic acidosis with delta lactate at 6 hours
Time Frame: 6 hours
|
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
|
6 hours
|
Number of patients with effect of ejection fraction / cardiac outout on delta arterial lactate at 6 hours
Time Frame: 6 hours
|
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
|
7 days
|
The effect of need of renal replacement therapy (till day 7) on delta lactate at 6 hours
Time Frame: 7 days
|
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
|
7 days
|
The amount of fluid resuscitated and its effect on delta lactate at 6 hours
Time Frame: 7 days
|
7 days
|
Number of patients with number of patients with Noradrenaline requirement and effect on delta lactate at 6 hours
Time Frame: 7 days
|
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
|
28 days
|
Coerrelation between presence or absence of respiratory acidosis on the delta lactate at 6 hours
Time Frame: 6 hours
|
6 hours
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ILBS-ACLF-13
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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