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Renal Insufficiency, ChronicSTRIPNCT02719418

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

An observational study of Renal Insufficiency, Chronic and Deep Venous Thrombosis, Protection Against, run by Maisonneuve-Rosemont Hospital at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tinzaparin
Type of treatment
Injection or infusion
How many people
28 participants
Where
1 siteCanada
Study dates
1 Feb 2016to 12 Dec 2018
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 11Show fewer
  • Acute renal failure in an individual with baseline eGFR > 30 ml/min/1.73 m2
  • Prophylactic tinzaparin in use for more than 72h before inclusion
  • Severe liver insufficiency (Child- Pugh C)
  • Anuria or chronically dialysed patients (or eGFR < 5 ml/min/1.73 m2)
  • Participation in another study

Trial locations and contacts

1 site in 1 country.

Canada1 site
  • Maisonneuve-Rosemont Hospital

    Montreal, Quebec, H1T 2M4

Other trials in Canada

About this study

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.

Read the detailed description

STUDY DESIGN :

Prospective, monocentric, open-label, single-arm, observational cohort study

Subjects hospitalized for non-surgical reasons by medical departments (ie Nephrology, Pneumology, Cardiology and Internal medicine) with chronic kidney disease (baseline eGFR ≤30 ml/min/1.73 m2) receiving tinzaparin prophylaxis at a dose of 3500 IU (or 4500 IU if BMI > 30kg/m2) once-daily.

Pharmacokinetic parameters: Peak anti-Xa analyses done after 2 (or 3), 5, and 8 days of treatment, and one trough anti-Xa analysis on day 5. The bioaccumulation of tinzaparin will be assessed by determining whether this dosing regimen is associated with an excessive increase in anti-Xa levels over the course of the treatment (see below for statistical analysis).

RECRUITMENT PROCESS:

A systematic screening for potential study subjects will be made by the research coordinators based on key computer searches fields throughout four different softwares. Through these databases, researchers will be able to perform a preliminary selection of any of the eligible subjects by identifying hospitalized patients that will ultimately be treated. The pharmacists responsible for validation of tinzaparin prescriptions at the pharmacy department will work with the research team at the initial screening by identifying eligible candidates. Since the choice of prescribed agents is to the prescriber's discretion, the recruitment procedures will be triggered mainly as soon as a prescription of tinzaparin at thromboprophylaxic dose is written.Subjects who meet the inclusion criteria and do not meet any exclusion criteria will be considered eligible candidates and additional baseline information will be collected at that point, such as ethnicity and sex. The eligible participant will be addressed directly by a member of the research team. Informed consent will be sought and documented through the Information Form and Informed Consent (FIC) already approved by the ethics committee the hospital.

DATA COLLECTION:

Four blood samples, three of which will be collected 4±1 hours after the injection of tinzaparin at days 2 (or 3), at day 5 and at day 8, and one trough that will be collected at day 5.

Pre-identified tubes (encoded) will be provided to the nursing and the sample shipping staff with specific instructions for manipulation of the blood sample and shipping to the laboratory.

STUDY SAMPLE:

In this study, it is considered that bioaccumulation should be statistically significant if Cmax of anti-Xa are increased by at least 20%. Estimation of the population size was performed using information obtained from Mahé et al. due to the similar nature of the population studied. As for mean plasma anti-Xa peak levels, a study done by Bara L et al. showed that 431 patients receiving 3 500 IU of tinzaparin for thromboprophylaxis had a mean of 0.15 IU/ml, which is the dose that will be given to most of the subjects in the present study. Based on the coefficient variation of Mahé et al. of 0.36 and the mean plasma anti-Xa level found by Bara L. et al, a standard deviation of 0.05 IU/ml was established, considering that the same coefficient of variation should be maintained across the dose administered. For the purpose of this study, researchers presumed an identical variance between all anti-Xa levels regardless of the day of blood sample collection. According to the null hypothesis, the mean of the distribution is 0.15 IU/ml while for the alternative hypothesis; the average would be 0.18 IU/ml (since established cut-off is a 20% increase). With a paired one-tailed t test, an alpha error of 0.05, a power of 0.90, and a strong correlation between measurements (r=0.7) , 25 participants are required to detect an increase ≥ 20% in anti-Xa activity between sampling on day 2 or 3 and at maximum of 8 days.

Being tested
Tinzaparin
Keywords
Thromboembolism, Venous Thrombosis, Embolism and Thrombosis, Chronic Renal Diseases, Kidney Failure, Chronic, Renal Failure, Chronic, Venous Thromboembolism, Tinzaparin, Innohep, Heparin, Low-Molecular-Weight
Medical subject headings
Renal Insufficiency, Chronic, Venous Thrombosis, Thromboembolism, Embolism and Thrombosis, Kidney Failure, Chronic, Venous Thromboembolism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TinzaparinDrug

    Also called Innohep

    3500 Unit or 4500 Unit subcutaneous once daily

Study groups in NCT02719418
Study groupRoleWhat they receive
TinzaparinHospitalized 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.
Receives: Drug: Tinzaparin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (3)
  1. Peak anti-Xa levels in patients with eGFR ≤ 20 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 Cmax of tinzaparin of the anti-Xa activity.

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

  2. 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 8 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 Cmax of tinzaparin anti-Xa activity.

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

  3. Anti-Xa trough level

    To explore the safety of tinzaparin at daily prophylactic doses for VTE in renally impaired patients by measuring the trough anti-Xa level (Cmin) on day 5, and to assess the proportion of participants with a trough above 0.40 IU/mL. A level of just above 0.50 IU/ml anti-Xa activity (close to 0.4 IU/ml) is within the range of therapeutic anticoagulation for the treatment of VTE with tinzaparin and, therefore, is considered excessive anticoagulation for VTE prophylaxis.

    Measured: On day 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2016 (estimated)
  2. Study start1 Feb 2016
  3. Primary completion30 Sep 2016
  4. Study completion12 Dec 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02719418
Sponsor's protocol ID
STRIP-001
Acronym
STRIP
Status last verified
Dec 2018
First submitted
14 Mar 2016
Last updated
13 Dec 2018
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • Turpie AG, Leizorovicz A. Prevention of venous thromboembolism in medically ill patients: a clinical update. Postgrad Med J. 2006 Dec;82(974):806-9. doi: 10.1136/pgmj.2005.044107.

    PubMed 17148703
  • Goldhaber SZ, Dunn K, MacDougall RC. New onset of venous thromboembolism among hospitalized patients at Brigham and Women's Hospital is caused more often by prophylaxis failure than by withholding treatment. Chest. 2000 Dec;118(6):1680-4. doi: 10.1378/chest.118.6.1680.

    PubMed 11115458
  • Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, Cook DJ, Balekian AA, Klein RC, Le H, Schulman S, Murad MH. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e195S-e226S. doi: 10.1378/chest.11-2296.

    PubMed 22315261
  • Office of the Surgeon General (US); National Heart, Lung, and Blood Institute (US). The Surgeon General's Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism. Rockville (MD): Office of the Surgeon General (US); 2008. Available from http://www.ncbi.nlm.nih.gov/books/NBK44178/

    PubMed 20669525
  • Parikh AM, Spencer FA, Lessard D, Emery C, Baylin A, Linkletter C, Goldberg RJ. Venous thromboembolism in patients with reduced estimated GFR: a population-based perspective. Am J Kidney Dis. 2011 Nov;58(5):746-55. doi: 10.1053/j.ajkd.2011.06.021. Epub 2011 Aug 27.

    PubMed 21872977
  • Pavord S, Myers B. Bleeding and thrombotic complications of kidney disease. Blood Rev. 2011 Nov;25(6):271-8. doi: 10.1016/j.blre.2011.07.001. Epub 2011 Aug 26.

    PubMed 21872374
  • Bottger B, Wehling M, Bauersachs RM, Amann S, Schuchert A, Reinhold C, Kumpers P, Wilke T. Prevalence of renal insufficiency in hospitalised patients with venous thromboembolic events: a retrospective analysis based on 6,725 VTE patients. Thromb Res. 2014 Nov;134(5):1014-9. doi: 10.1016/j.thromres.2014.09.003. Epub 2014 Sep 9.

    PubMed 25263017
  • Cook D, Arabi Y, Ferguson N, Heels-Ansdell D, Freitag A, McDonald E, Clarke F, Keenan S, Pagliarello G, Plaxton W, Herridge M, Karachi T, Vallance S, Cade J, Crozier T, Alves da Silva S, Costa Filho R, Brandao N, Watpool I, McArdle T, Hollinger G, Mandourah Y, Al-Hazmi M, Zytaruk N, Adhikari NK; PROTECT Research Coordinators; PROTECT Investigators; Canadian Critical Care Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group. Physicians declining patient enrollment in a critical care trial: a case study in thromboprophylaxis. Intensive Care Med. 2013 Dec;39(12):2115-25. doi: 10.1007/s00134-013-3074-x.

    PubMed 24022796
  • PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group; Cook D, Meade M, Guyatt G, Walter S, Heels-Ansdell D, Warkentin TE, Zytaruk N, Crowther M, Geerts W, Cooper DJ, Vallance S, Qushmaq I, Rocha M, Berwanger O, Vlahakis NE. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011 Apr 7;364(14):1305-14. doi: 10.1056/NEJMoa1014475. Epub 2011 Mar 22.

    PubMed 21417952
  • Folsom AR, Lutsey PL, Astor BC, Wattanakit K, Heckbert SR, Cushman M; Atherosclerosis Risk in Communities Study. Chronic kidney disease and venous thromboembolism: a prospective study. Nephrol Dial Transplant. 2010 Oct;25(10):3296-301. doi: 10.1093/ndt/gfq179. Epub 2010 Mar 29.

    PubMed 20353958
  • Wattanakit K, Cushman M. Chronic kidney disease and venous thromboembolism: epidemiology and mechanisms. Curr Opin Pulm Med. 2009 Sep;15(5):408-12. doi: 10.1097/MCP.0b013e32832ee371.

    PubMed 19561505
  • Christiansen CF, Schmidt M, Lamberg AL, Horvath-Puho E, Baron JA, Jespersen B, Sorensen HT. Kidney disease and risk of venous thromboembolism: a nationwide population-based case-control study. J Thromb Haemost. 2014 Sep;12(9):1449-54. doi: 10.1111/jth.12652. Epub 2014 Jul 29.

    PubMed 25040558
  • Ocak G, Vossen CY, Verduijn M, Dekker FW, Rosendaal FR, Cannegieter SC, Lijfering WM. Risk of venous thrombosis in patients with major illnesses: results from the MEGA study. J Thromb Haemost. 2013 Jan;11(1):116-23. doi: 10.1111/jth.12043.

    PubMed 23106832
  • Kumar G, Sakhuja A, Taneja A, Majumdar T, Patel J, Whittle J, Nanchal R; Milwaukee Initiative in Critical Care Outcomes Research (MICCOR) Group of Investigators. Pulmonary embolism in patients with CKD and ESRD. Clin J Am Soc Nephrol. 2012 Oct;7(10):1584-90. doi: 10.2215/CJN.00250112. Epub 2012 Jul 26.

    PubMed 22837271
  • Fanikos J, Stevens LA, Labreche M, Piazza G, Catapane E, Novack L, Goldhaber SZ. Adherence to pharmacological thromboprophylaxis orders in hospitalized patients. Am J Med. 2010 Jun;123(6):536-41. doi: 10.1016/j.amjmed.2009.11.017.

    PubMed 20569760

Questions about this trial

What is this clinical trial studying?

An observational study of Renal Insufficiency, Chronic and Deep Venous Thrombosis, Protection Against, run by Maisonneuve-Rosemont Hospital at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak anti-Xa levels in patients with eGFR ≤ 30 mL/min/1.73 m2 receiving repeated daily doses of tinzaparin for VTE prophylaxis (time frame: 4±1 hours after administration of tinzaparin on days 2 or 3, and 5.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02719418, which also lists 39 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2018.

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