Study of the Bioaccumulation of Tinzaparin in Renally Impaired Patients When Given at Prophylactic Doses

NCT02719418 | Completed

• 1 other identifier: STRIP-001
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess if accumulation of anti-Xa activity occurs after repeated daily administration of prophylactic doses of tinzaparin in patients with severe chronic kidney disease (CKD) requiring thromboprophylaxis for non-surgical conditions. It is anticipated that tinzaparin used at a fixed dose for thromboprophylaxis in severe CKD patients (eGFR ≤ 30 ml/min /1.73 m2) at risk for venous thromboembolism (VTE) will not bioaccumulate at a significant level, meaning an increase of ≥ 20% of the anti-Xa mean level between day 2 or 3 and day 5.

Conditions

Renal Insufficiency, Chronic; Deep Venous Thrombosis, Protection Against

Keywords

Thromboembolism; Venous Thrombosis; Embolism and Thrombosis; Chronic Renal Diseases; Kidney Failure, Chronic; Renal Failure, Chronic; Venous Thromboembolism; Tinzaparin; Innohep; Heparin, Low-Molecular-Weight

Outcome Measures

Primary Outcomes (1)

• Peak anti-Xa levels in patients with eGFR ≤ 30 mL/min/1.73 m2 receiving repeated daily doses of tinzaparin for VTE prophylaxis

  To compare the anti-Xa levels between day 2 (or 3) and day 5 in order to assess if bioaccumulation occurs at a significant level, meaning an increase of ≥ 20% of the anti-Xa mean level.The anti-Xa levels will be measured 4±1 hours after administration, which corresponds to the maximal concentration (Cmax) of tinzaparin anti-Xa activity.

  4±1 hours after administration of tinzaparin on days 2 or 3, and 5.

Secondary Outcomes (3)

• Peak anti-Xa levels in patients with eGFR ≤ 20 mL/min/1.73 m2 receiving repeated daily doses of tinzaparin for VTE prophylaxis

  4±1 hours after administration of tinzaparin on days 2 or 3, and 5.

• Peak anti-Xa levels in patients with eGFR ≤ 30 mL/min/1.73 m2 receiving repeated daily doses of tinzaparin for VTE prophylaxis

  4±1 hours after administration of tinzaparin on days 2 or 3, and 8.

• Anti-Xa trough level

  On day 5

Other Outcomes (1)

• Bleeding events or thrombotic events

  From time of entry in the study to end of study (maximum of 8 days)

Study Arms (1)

Tinzaparin

Hospitalized patients with chronic renal insufficiency (eGFR ≤ 30 mL/min/1.73 m2) at risk of VTE secondary to non-surgical reasons and receiving thromboprophylactic doses of tinzaparin 3500 or 4500 unit sub-cutaneous once daily.

Drug: Tinzaparin

Interventions

Tinzaparin DRUG

3500 Unit or 4500 Unit subcutaneous once daily

Also known as: Innohep

Tinzaparin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects with severe renal impairment (eGFR ≤ 30 mL/min/1.73 m2) at risk of VTE secondary to non-surgical reasons and receiving thromboprophylactic doses of tinzaparin. The study sample will be selected from patients that are hospitalized by medical departments (i.e. nephrology, internal medicine, cardiology, pneumology) and on the transitional hospitalization unit.

You may qualify if:

• Age ≥ 18 years old
• A prescription of prophylactic tinzaparin (3500 IU or 4500 IU) has been initiated by order of the treating physician
• Patient admitted for medical reasons by one (but not limited to) of the following wards: nephrology, internal medicine, cardiology or pneumology
• Chronic severe renal impairment defined as an eGFR ≤ 30 mL/min/1.73 m2 at the moment of prescription and when available, eGFR at baseline, ie ≤ 30 ml/min/1.73 m2 for the last 3 months
• Estimated length of stay ≥ 5 days
• Written informed consent obtained within at most 3 ± 1 hours after the second or third dose of tinzaparin.

You may not qualify if:

• Super obese (Body-mass Index (BMI) \> 50kg/m2)
• Treatment with UFH, LMWH or oral factor Xa inhibitors \<48h prior starting the first dose of tinzaparin
• Prophylaxis with LMWH other than tinzaparin \< 48h prior starting the first dose of tinzaparin
• Prophylaxis with heparin \< 12h prior starting the first dose of tinzaparin
• Treatment with argatroban, bivalirudin \< 24 hours prior starting the first dose of tinzaparin
• Treatment with oral direct thrombin inhibitors, danaparoid, fondaparinux, or anti-vitamin K agents for \< 7 days prior to starting the first dose of tinzaparin
• Acute renal failure in an individual with baseline eGFR \> 30 ml/min/1.73 m2
• Severe liver insufficiency (Child- Pugh C)
• Anuria or chronically dialysed patients (or eGFR \< 5 ml/min/1.73 m2)
• Participation in another study

Sponsors & Collaborators

• Maisonneuve-Rosemont Hospital: lead

Study Sites (1)

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

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Biospecimen

Retention: SAMPLES WITH DNA

Whole blood

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Venous Thrombosis; Thromboembolism; Embolism and Thrombosis; Kidney Failure, Chronic; Venous Thromboembolism

Interventions

Tinzaparin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Jean-Philippe Lafrance

  Maisonneuve-Rosemont Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD., M.Sc., FRCPC

Study Record Dates

• First Submitted: March 14, 2016
• First Posted: March 25, 2016
• Study Start: February 1, 2016
• Primary Completion: September 30, 2016
• Study Completion: December 12, 2018
• Last Updated: December 13, 2018

Record last verified: 2018-12

Locations

CA (1)