Ignite Creation Date:
2024-05-05 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00138099
Status:
COMPLETED
Last Update Posted:
2007-06-01
First Post:
2005-08-29
Brief Title:
Dalteparins Influence on Renally Compromised Anti-Ten-A Study DIRECT
Sponsor:
Hamilton Health Sciences Corporation
Organization:
McMaster University
Study Overview
Official Title:
Dalteparins Influence on Renally Compromised Anti-Ten-A Study DIRECT
Status:
COMPLETED
Status Verified Date:
2006-11
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:
The investigators primary research objective is
To determine the safety of dalteparin prophylaxis 5000 IU once-daily in Intensive Care Unit ICU patients based on
the proportion of patients with trough anti-Xa 040 IUmL during dalteparin prophylaxis after 3 1 days 10 1 days and 17 1 days of dalteparin prophylaxis
the risk of major bleeding during the treatment period
The investigators secondary research objectives are
To determine the pharmacokinetic properties of dalteparin prophylaxis in ICU patients with severe renal insufficiency
To identify clinical and laboratory factors that predict an excessive anticoagulant effect anti-Xa 010 IUmL
To estimate the relationship between trough anti-Xa levels and bleeding
The DIRECT Pilot Study
Before embarking on a large trial of low molecular weight heparin LMWH versus standard unfractionated heparin UFH the DIRECT Study is needed to observe whether bioaccumulation of LMWH occurs in ICU patients with moderate to severe renal insufficiency and to address potential problems with protocol implementation
To determine the safety of dalteparin prophylaxis 5000 IU once-daily in Intensive Care Unit ICU patients based on
the proportion of patients with trough anti-Xa 040 IUmL during dalteparin prophylaxis after 3 1 days 10 1 days and 17 1 days of dalteparin prophylaxis
the risk of major bleeding during the treatment period
The investigators secondary research objectives are
To determine the pharmacokinetic properties of dalteparin prophylaxis in ICU patients with severe renal insufficiency
To identify clinical and laboratory factors that predict an excessive anticoagulant effect anti-Xa 010 IUmL
To estimate the relationship between trough anti-Xa levels and bleeding
The DIRECT Pilot Study
Before embarking on a large trial of low molecular weight heparin LMWH versus standard unfractionated heparin UFH the DIRECT Study is needed to observe whether bioaccumulation of LMWH occurs in ICU patients with moderate to severe renal insufficiency and to address potential problems with protocol implementation
Detailed Description:
Critically ill patients who are admitted to an intensive care unit ICU are at high risk for deep vein thrombosis DVT with an estimated 20-40 of patients developing DVT without prophylaxis Preventing DVT is important because DVT is usually clinically silent in such patients and its first manifestation may be life-threatening pulmonary embolism
About 30 of ICU patients have renal insufficiency based on a calculated creatinine clearance CrCl and such patients have 4-fold higher risk of DVT than those with normal renal function
The current anticoagulant regimen that is used to prevent DVT in such patients consisting of unfractionated heparin UFH 5000 IU twice-daily may be inadequate
A recent prospective cohort study by our research group that investigated the risk of DVT in 261 ICU patients found that 10 of patients developed proximal vein DVT after admission to the ICU despite receiving UFH 5000 IU twice-daily
In other patient groups at high risk for DVT low-molecular-weight heparins LMWHs have replaced UFH for DVT prophylaxis because of superior efficacy
Despite superior efficacy and safety in many patients there is concern about using LMWHs in patients with renal insufficiency because LMWHs are cleared by the kidney LMWH use in such patients might result in an excessive anticoagulant effect with the potential to increase bleeding
Much of the concern about the safety of LMWH in patients with renal insufficiency pertains to therapeutic-dose LMWH used to treat DVT Prophylactic-or low dose LMWH that is used to prevent DVT in ICU patients is about 25-33 of a therapeutic-dose
Three sources of evidence suggest that prophylactic-dose LMWH may be safe in patients with renal insufficiency First current evidence does not support the fact that prophylactic-dose LMWH accumulates and should be avoided in such patients Second prophylactic-dose LMWH appears to be safe in hemodialysis patients Third preliminary work by our research group suggests that dalteparin 5000 IU once-daily does not accumulate in ICU patients with renal insufficiency Thus 0 of 10 ICU patients with a CrCl 50 mLmin173m2 who received dalteparin had a detectable trough anticoagulant effect anti-Xa 010 IUmL Further when the relationship between CrCl and peak anti-Xa levels was assessed there was no correlation r02 Finally in 2 patients with severe renal insufficiency CrCl30 mLmin173m2 who received dalteparin 5000 IU once-daily all 9 trough anti-Xa values were 010 IUmL
No study has investigated the safety of low-dose LMWH in ICU patients with impaired renal function until such a study is completed randomized trials assessing the efficacy of low-dose LMWH for DVT prophylaxis among ICU patients will not be feasible
As a first step in addressing this problem we propose an open-label pilot study to assess the safety of dalteparin prophylaxis 5000 IU once-daily in ICU patients with severe renal insufficiency
The safety of the proposed dalteparin prophylaxis regimen will be assessed by determining the risk of an excessive anticoagulant effect and the risk of major bleeding Dalteparin prophylaxis will be considered safe if 2 criteria are satisfied by the end of the treatment period
proportion of patients with trough anti-Xa level 040 IUmL is 10 or less exclude 17 with 95 confidence
risk of major bleeding is 4 or less exclude 10 with 95 confidence
If we show that dalteparin prophylaxis is safe in ICU patients with severe renal insufficiency this will improve patient care in 2 ways
dalteparin may reduce the risk of DVT although this should be tested in future trials and
dalteparin would reduce heparin induced thrombocytopenia HIT an infrequent but serious complication of UFH
About 30 of ICU patients have renal insufficiency based on a calculated creatinine clearance CrCl and such patients have 4-fold higher risk of DVT than those with normal renal function
The current anticoagulant regimen that is used to prevent DVT in such patients consisting of unfractionated heparin UFH 5000 IU twice-daily may be inadequate
A recent prospective cohort study by our research group that investigated the risk of DVT in 261 ICU patients found that 10 of patients developed proximal vein DVT after admission to the ICU despite receiving UFH 5000 IU twice-daily
In other patient groups at high risk for DVT low-molecular-weight heparins LMWHs have replaced UFH for DVT prophylaxis because of superior efficacy
Despite superior efficacy and safety in many patients there is concern about using LMWHs in patients with renal insufficiency because LMWHs are cleared by the kidney LMWH use in such patients might result in an excessive anticoagulant effect with the potential to increase bleeding
Much of the concern about the safety of LMWH in patients with renal insufficiency pertains to therapeutic-dose LMWH used to treat DVT Prophylactic-or low dose LMWH that is used to prevent DVT in ICU patients is about 25-33 of a therapeutic-dose
Three sources of evidence suggest that prophylactic-dose LMWH may be safe in patients with renal insufficiency First current evidence does not support the fact that prophylactic-dose LMWH accumulates and should be avoided in such patients Second prophylactic-dose LMWH appears to be safe in hemodialysis patients Third preliminary work by our research group suggests that dalteparin 5000 IU once-daily does not accumulate in ICU patients with renal insufficiency Thus 0 of 10 ICU patients with a CrCl 50 mLmin173m2 who received dalteparin had a detectable trough anticoagulant effect anti-Xa 010 IUmL Further when the relationship between CrCl and peak anti-Xa levels was assessed there was no correlation r02 Finally in 2 patients with severe renal insufficiency CrCl30 mLmin173m2 who received dalteparin 5000 IU once-daily all 9 trough anti-Xa values were 010 IUmL
No study has investigated the safety of low-dose LMWH in ICU patients with impaired renal function until such a study is completed randomized trials assessing the efficacy of low-dose LMWH for DVT prophylaxis among ICU patients will not be feasible
As a first step in addressing this problem we propose an open-label pilot study to assess the safety of dalteparin prophylaxis 5000 IU once-daily in ICU patients with severe renal insufficiency
The safety of the proposed dalteparin prophylaxis regimen will be assessed by determining the risk of an excessive anticoagulant effect and the risk of major bleeding Dalteparin prophylaxis will be considered safe if 2 criteria are satisfied by the end of the treatment period
proportion of patients with trough anti-Xa level 040 IUmL is 10 or less exclude 17 with 95 confidence
risk of major bleeding is 4 or less exclude 10 with 95 confidence
If we show that dalteparin prophylaxis is safe in ICU patients with severe renal insufficiency this will improve patient care in 2 ways
dalteparin may reduce the risk of DVT although this should be tested in future trials and
dalteparin would reduce heparin induced thrombocytopenia HIT an infrequent but serious complication of UFH
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| Control No 092103 | None | None | None |
| File No 9427-M1133-21C | None | None | None |