Safety Study of Enoxaparin Prophylaxis in Critically Ill Adults With Severe Renal Insufficiency

Hemorrhage Clinical Trial

Official title:

Phase 4 Study Determining the Safety of Enoxaparin Prophylaxis in Critically Ill Adults With Severe Renal Insufficiency

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02690090
• Other study ID #: Enox-TOH-0001-RP
• Status: Recruiting
• Phase: Phase 4
• First received: January 10, 2014
• Last updated: February 18, 2016
• Start date: February 2014
• Est. completion date: December 2016

Study information

• Verified date: February 2016
• Source: Ottawa Hospital Research Institute
• Contact: Rakesh V Patel, M.D.
• Phone: 613.737.8899
• Email: rpatel[@]toh.on.ca
• Is FDA regulated: No
• Health authority: Canada: Ethics Review CommitteeCanada: Health Canada
• Study type: Observational

Clinical Trial Summary

The investigators study is the first step (a pilot study) in determining whether the manufacturer's recommended dose of a blood thinner called enoxaparin, in adults who are patients in an intensive care unit and have severely reduced kidney function (less than or equal to approximately 30% of their normal function) is safe with respect to the adverse effect of bleeding.

The investigators hypothesis is that studying these patients, going forward in time, without interfering with their care, to eventually determine if this blood thinner is safe at reduced doses, is feasible.

Description:

Objectives:

To determine the feasibility of conducting a single centre, open-label, prospective study to inform preparation for a prospective phase III study evaluating the efficacy & safety of enoxaparin prophylaxis in critically ill adults with creatinine clearance < 30 mL/min.

Study Design:

A pilot open-label, single-arm, prospective study.

Patients:

Critically ill adults (> 18 years) with creatinine clearance < 30 mL/min.

Setting:

The Ottawa Hospital Intensive Care Units

Sample Size: n=30.

Intervention:

Study patients will receive enoxaparin 30 mg S.C. daily for VTE prophylaxis as directed by their responsible Intensivist. The investigators are not directing this clinical intervention in any manner.

Primary/Feasibility Outcomes: screening and enrolment rates with a goal of recruiting at least 5 patients collectively, from both ICUs, per month.

Secondary/Clinical Outcomes: Determining the accumulation of anti-Xa concentrations, if any, recording of the rates of major bleeding, VTE, and HIT during the study.

Trial Duration:

Anticipated 24 months.

Analysis:

Statistical analysis will be performed using SAS software through the Ottawa Hospital Methods Centre. Patient demographics and clinical baseline characteristics will be described. Continuous variables will be presented as mean (SD), ordinal variables as medians (IQR) and categorical variables as proportions. Cox proportional hazards analysis will be used to evaluate an association between trough anti-Xa levels and major bleeding.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• body weight = 45 kg

• expected ICU length of stay = 72 hours

• severe renal insufficiency, defined by calculated creatinine clearance (CrCl) < 30 mL/min using the Cockcroft-Gault formula

• All patients with severe renal insufficiency at ICU admission will be included, regardless of chronicity of renal disease. This includes patients with pre-existing dialysis dependence via intermittent hemodialysis and peritoneal dialysis; patients with acute kidney injury requiring SLED (sustained low-efficiency dialysis) will also be included.

Exclusion Criteria:

• neurological surgery in last 3 months

• epidural catheter insertion within previous 12 hours

• ICU admission > 2 weeks

• receipt of > 2 doses of LMWH while in ICU or in hospital within 7 days prior to study enrolment

• active bleeding; platelet count < 50 x 109/L

• INR or aPTT > 2 times the upper limit of normal

• need for therapeutic anticoagulation; previous adverse reaction to heparin based products

• contraindication to blood product transfusion

• pregnant or lactating women

• life expectancy < 2 weeks or receiving palliative care

• previous enrolment in current study.

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Critical Illness
• Hemorrhage
• Renal Insufficiency

Locations

Country	Name	City	State
Canada	The Ottawa Hospital	Ottawa	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	The Ottawa Hospital

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the rate of patient enrollment into this study within the 24 month allotted time frame of recruitment	This is a pilot feasibility study	24 months	No
Secondary	Measure bioaccumulation of Enoxaparin, if any, defined as at least one trough anti-Xa level measuring > 0.4 IU/mL	Trough Anti-Xa concentration at baseline, 4, 8, 12, 16 & 24 hours of ICU day 1	24 hours	Yes
Secondary	Record incidence of major bleeding episodes using the HEME bleeding assessment tool		Daily until ICU discharge or a maximum of the first 10 days of ICU stay, whichever is less	Yes
Secondary	Record incidence of VTE		Daily until ICU discharge or a maximum of the first 10 days of ICU stay, whichever is less	Yes
Secondary	Measure bioaccumulation of Enoxaparin, if any, defined as at least one trough anti-Xa level measuring > 0.4 IU/mL	Trough Anti-Xa concentration will be measured on days; 2, 3, 4, 7 & day of ICU discharge or ICU day 10, whichever is less	ICU stay until discharge or a maximum of the first 10 days of ICU stay, whichever is less	Yes