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

Sponsor

Ottawa Hospital Research Institute (Other)

Overall Status

Unknown status

CT.gov ID

NCT02690090

Collaborator

The Ottawa Hospital (Other)

Enrollment

Location

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Hemorrhage

Detailed 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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Feb 1, 2014

Anticipated Primary Completion Date :

Mar 1, 2016

Anticipated Study Completion Date :

Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
enoxaparin enoxaparin prophylaxis as directed by treating Intensivist

Outcome Measures

Primary Outcome Measures

Determine the rate of patient enrollment into this study within the 24 month allotted time frame of recruitment [24 months]
This is a pilot feasibility study

Secondary Outcome Measures

Measure bioaccumulation of Enoxaparin, if any, defined as at least one trough anti-Xa level measuring > 0.4 IU/mL [24 hours]
Trough Anti-Xa concentration at baseline, 4, 8, 12, 16 & 24 hours of ICU day 1
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]
Record incidence of VTE [Daily until ICU discharge or a maximum of the first 10 days of ICU stay, whichever is less]
Measure bioaccumulation of Enoxaparin, if any, defined as at least one trough anti-Xa level measuring > 0.4 IU/mL [ICU stay until discharge or a maximum of the first 10 days of ICU stay, whichever is less]
Trough Anti-Xa concentration will be measured on days; 2, 3, 4, 7 & day of ICU discharge or ICU day 10, whichever is less

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.