Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06515145
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-06-18
Brief Title:
High-volume Versus Standard Volume Plasma Exchange in Patients With Acute Liver Failure With Cerebral Edema
Sponsor:
None
Organization:
None
Study Overview
Official Title:
To Evaluate the Safety and Efficacy of High-volume Versus Standard Volume Plasma Exchange in Patients With Acute Liver Failure With Cerebral Edema -A Prospective Randomized Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In this prospective randomized controlled trial Investigator aim to evaluate the impact of high versus standard volume plasma-exchange in patients with acute liver failure with cerebral edema and clinical outcomes ALF who meet the inclusion and exclusion criteria within the first 12 hours will be randomized into two groups
Interventional - High-volume plasma exchange Active Comparator - Standard volume plasma exchange
Expected outcome of the project-
1 Primary end points Time to improvement in cerebral edema
2 Secondary end points
To study the adverse events of therapy volume overload pulmonary complications allergic reactions etc
Transplant-free survival at day 21
Interventional - High-volume plasma exchange Active Comparator - Standard volume plasma exchange
Expected outcome of the project-
1 Primary end points Time to improvement in cerebral edema
2 Secondary end points
To study the adverse events of therapy volume overload pulmonary complications allergic reactions etc
Transplant-free survival at day 21
Detailed Description:
All patients will undergo plain CT-scan of the brain to screen for the presence and severity of cerebral edema in the emergency before being shifted to the L-ICU In the L- ICU patients will be managed by a multidisciplinary team Intubation and ventilation will be undertaken for standard indications in addition to the development of grade 3 encephalopathy or evidence of cerebral edema on CT-scan Ventilation will be managed by fentanyl and propofol along with the use of atracurium for paralysis wherever required All patients will be monitored constantly for macro-hemodynamics global tissue perfusion and microcirculation The macro-hemodynamic parameters included continuous monitoring of mean arterial pressure MAP heart rate and urine output per hour The real-time monitoring of systemic vascular resistance SVR stroke volume variation SVV cardiac index CI and cardiac output CO will be done by a hemodynamic monitor FloTrac system 40 Edwards Lifesciences California US wherever feasible Global tissue perfusion adequacy and indirect assessment of microcirculation will be done by measurement of arterial lactate Fluid management will be done with crystalloids with the use of colloids 5 albumin in patients with severe hypoalbuminemia serum albumin less than 25gmdl Norepinephrine will be the primary vasopressor used to target a mean arterial pressure of 65-70 mm of Hg with adjunctive use of intravenous low dose hydrocortisone and vasopressin in patients not responsive to initial therapy
Cerebral edema The monitoring of cerebral edema will be performed measuring the optic nerve sheath diameter ONSD in both the eyes using a 75 MHz probe every 6-8 hours Apart from this routine monitoring of pupillary size and reactions extensor posturing and plantar reflexes will be performed every 6-8 hrs Transcranial doppler would be done every 6-8 hours Patients will receive 3 hypertonic saline as a continuous infusion initially started at 25ml hr and titrated 6 hourly to between 5 and 20 mL per hour maximum 100 mlhour to achieve serum sodium levels between 145-150 mmolL Intravenous 20 mannitol 1 gkg IV bolus over 20 to 30 minutes will be administered to those without renal failure All patients will in addition receive intravenous N-acetylcysteine for 5 dayRoutine electroencephalogram EEG will be done for all patients daily to screen for non-convulsive seizures which will be managed by intravenous levetiracetam Assessment of coagulation will be performed by ROTEM at baseline and subsequently as required
Protocol for therapeutic plasma-exchange TPE procedures will be performed using either Spectra Optia SPO Terumo BCT Lakewood CO USA continuous-flow centrifugal apheresis system or Haemonetics MCS Braintree MA USA intermittent flow centrifugal apheresis system via a double-lumen central venous dialysis catheter All patients will receive plasma-exchange within first 12 hours of admission to the L-ICU along with a target volume of based on the randomization group per session The replacement fluid used will be 90 FFP and 10 normal saline TPE will be performed on consecutive days until the desired response is achieved using our previously published protocol
The number of sessions of TPE in each patient will be decided based on the clinical response to SVPE Dynamic assessment of the clinical parameters signs of CE as assessed by pupillary size reaction and optic nerve-sheath diameter INR lactate and arterial ammonia will be performed at after each TPE In patients with an improvement in INR and signs of CE along with a reduction in ammonia at 6 hours which was sustained at 12 and 24 hours post-TPE subsequent sessions will be discontinued TPE will also be discontinued in patients who would show worsening in either clinical and or biochemical parameters In patients who will develop adverse events the TPE procedure will be resumed or discontinued depending on the severity of adverse event and its resolution CRRT would be initiated in patients who develop worsening or ammonia or cerebral edema or metabolic complications and time to initiation of CRRT would be recorded in both groups The time to initiation of CRRT would be recorded in both groups after randomization
Continuous renal replacement therapy will be administered as continuous venovenous hemodiafiltration CVVHDF using Prisma and Prismaflex Gambro devices with blood flows ranging from 150-180 mLhr and target effluent rates of 20 - 25 mLkghr Anticoagulation was not used during dialysis CRRT would be continued until resolution of cerebral edema and in decrease in ammonia levels below 150 ugdl or in those who develop adverse effects of therapy
Randomization will be done by taking 11 ratio by computer-generated sealed envelopes by the clinical trial co-ordinator
Intervention group High Volume PLsma Exchange HVPE Standard Medical Treatment SMT The high-volume strategy would be performed by centrifugation technique 8-9 litres of plasma would be exchanged in each patient over 6-8 hours
Active Comparator - The Standard volume Plasma Exchange Standard medical Treatment The Standard volume strategy group Therapeutic Plasma Exchange would be performed varying from 15- 25 times the plasma - volume
Cerebral edema The monitoring of cerebral edema will be performed measuring the optic nerve sheath diameter ONSD in both the eyes using a 75 MHz probe every 6-8 hours Apart from this routine monitoring of pupillary size and reactions extensor posturing and plantar reflexes will be performed every 6-8 hrs Transcranial doppler would be done every 6-8 hours Patients will receive 3 hypertonic saline as a continuous infusion initially started at 25ml hr and titrated 6 hourly to between 5 and 20 mL per hour maximum 100 mlhour to achieve serum sodium levels between 145-150 mmolL Intravenous 20 mannitol 1 gkg IV bolus over 20 to 30 minutes will be administered to those without renal failure All patients will in addition receive intravenous N-acetylcysteine for 5 dayRoutine electroencephalogram EEG will be done for all patients daily to screen for non-convulsive seizures which will be managed by intravenous levetiracetam Assessment of coagulation will be performed by ROTEM at baseline and subsequently as required
Protocol for therapeutic plasma-exchange TPE procedures will be performed using either Spectra Optia SPO Terumo BCT Lakewood CO USA continuous-flow centrifugal apheresis system or Haemonetics MCS Braintree MA USA intermittent flow centrifugal apheresis system via a double-lumen central venous dialysis catheter All patients will receive plasma-exchange within first 12 hours of admission to the L-ICU along with a target volume of based on the randomization group per session The replacement fluid used will be 90 FFP and 10 normal saline TPE will be performed on consecutive days until the desired response is achieved using our previously published protocol
The number of sessions of TPE in each patient will be decided based on the clinical response to SVPE Dynamic assessment of the clinical parameters signs of CE as assessed by pupillary size reaction and optic nerve-sheath diameter INR lactate and arterial ammonia will be performed at after each TPE In patients with an improvement in INR and signs of CE along with a reduction in ammonia at 6 hours which was sustained at 12 and 24 hours post-TPE subsequent sessions will be discontinued TPE will also be discontinued in patients who would show worsening in either clinical and or biochemical parameters In patients who will develop adverse events the TPE procedure will be resumed or discontinued depending on the severity of adverse event and its resolution CRRT would be initiated in patients who develop worsening or ammonia or cerebral edema or metabolic complications and time to initiation of CRRT would be recorded in both groups The time to initiation of CRRT would be recorded in both groups after randomization
Continuous renal replacement therapy will be administered as continuous venovenous hemodiafiltration CVVHDF using Prisma and Prismaflex Gambro devices with blood flows ranging from 150-180 mLhr and target effluent rates of 20 - 25 mLkghr Anticoagulation was not used during dialysis CRRT would be continued until resolution of cerebral edema and in decrease in ammonia levels below 150 ugdl or in those who develop adverse effects of therapy
Randomization will be done by taking 11 ratio by computer-generated sealed envelopes by the clinical trial co-ordinator
Intervention group High Volume PLsma Exchange HVPE Standard Medical Treatment SMT The high-volume strategy would be performed by centrifugation technique 8-9 litres of plasma would be exchanged in each patient over 6-8 hours
Active Comparator - The Standard volume Plasma Exchange Standard medical Treatment The Standard volume strategy group Therapeutic Plasma Exchange would be performed varying from 15- 25 times the plasma - volume
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None