Ignite Creation Date:
2025-12-24 @ 2:54 PM
Ignite Modification Date:
2025-12-26 @ 11:37 PM
Study NCT ID:
NCT00430859
Status:
COMPLETED
Last Update Posted:
2012-04-02
First Post:
2007-02-01
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Bovine Intestinal Alkaline Phosphatase for the Treatment of Patients With Sepsis
Sponsor:
AM-Pharma
Organization:
Study Overview
Official Title:
A Pilot, Double-blind, Randomised, Placebo-controlled, Exploratory Study to Investigate the Safety and Effect of Bovine Intestinal Alkaline Phosphatase in Patients With Sepsis
Status:
COMPLETED
Status Verified Date:
2012-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Eligible patients will receive either AP or matching placebo in a double blind, randomized design and following a 2:1 ratio. All medication will be given in addition to standard care for sepsis patients. Patients will be followed for 28 days after the start of study medication administration. A blinded safety review of the study results will take place after the inclusion of 12 patients in the study.
Detailed Description:
Both bolus and continuous infusions were found to effectively reduce the LPS-induced pro-inflammatory cytokine TNFα in piglets. When AP was administered as a bolus (160 U/kg), the reduction of TNFα after administration of 10 μg/kg LPS in piglets was found to be in the order of 32%. When 100 U/kg of CIAP was administered as an infusion over 50 minutes, reaching steady state levels of 400 U/L, the reduction in TNFα after LPS challenge was substantially (70%), as compared to TNFα levels after LPS only. A series of these studies demonstrated that dosages of 100-120 U/kg administered over 50 minutes could effectively reduce LPS toxicity at steady state levels around 400 U/L, about a 10 fold of the normal alkaline phosphatase plasma levels (40 U/L in piglets). Furthermore, it is estimated that the above-mentioned dosages can effectively detoxify 10 μg LPS/kg in piglets, which represents an LPS-equivalent derived from about 1010 colony forming units (cfu) of E.coli. These amounts of circulating bacteria are not easily established in a sepsis patient. It is estimated (personal communication, Prof. S. van Deventer, Academic Medical Centre, Amsterdam) that the bacterial load in these patients is less than 107 bacteria total, which is equivalent to approx. 2x105 cfu/kg.
In summary, in piglets 160 U/kg AP was able to detoxify an amount of LPS equivalent to 1010 cfu E. Coli/kg, which is approximately 50,000 times the expected amount of bacteria in sepsis patients. We therefore expect that the dosage used in human (200 U/kg) administered over 24 hours is able to detoxify the amount of LPS present in sepsis patients. This dosage will result in 5-times normal plasma level of alkaline phosphatase which was well tolerated during the previous clinical trials. Since the effect of antibiotic treatment is expected to occur within hours of administration we decided to establish this steady state level of AP as fast as possible, which explains the initial bolus-like administration by short infusion, followed by a prolonged steady state infusion.
In summary, in piglets 160 U/kg AP was able to detoxify an amount of LPS equivalent to 1010 cfu E. Coli/kg, which is approximately 50,000 times the expected amount of bacteria in sepsis patients. We therefore expect that the dosage used in human (200 U/kg) administered over 24 hours is able to detoxify the amount of LPS present in sepsis patients. This dosage will result in 5-times normal plasma level of alkaline phosphatase which was well tolerated during the previous clinical trials. Since the effect of antibiotic treatment is expected to occur within hours of administration we decided to establish this steady state level of AP as fast as possible, which explains the initial bolus-like administration by short infusion, followed by a prolonged steady state infusion.
Study Oversight
Has Oversight DMC:
True
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| EudraCT No. 2005-005257-21 | None | None | View |