Prophylaxis of Thromboembolic Complications Trial: Thromboprophylaxis Needed in Below Knee Plaster Cast Immobilization for Ankle and Foot Fractures

Pulmonary Embolism Clinical Trial

— PROTECT  

Official title:

Prophylaxis of Venous Thromboembolism in Patients With a Nonsurgical Fracture of the Lower Extremity Immobilised in a Below-Knee Plaster Cast

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00881088
• Other study ID #: PROTECT
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: April 13, 2009
• Last updated: December 15, 2012
• Start date: April 2009
• Est. completion date: April 2013

Study information

• Verified date: May 2009
• Source: Red Cross Hospital Beverwijk
• Contact: Robert J Derksen, MD, PhD
• Phone: +31 6 24748122
• Email: rjderksen[@]hotmail.com
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Objective:

The purpose of this study is to determine the need for thromboprophylaxis in patients with a fracture of the lower extremity being treated conservatively in a below-knee plaster cast and to assess if both of the two tested prophylactic treatments are effective for this indication.

Hypothesis:

Nadroparine and Fondaparinux are both effective in preventing a thromboembolic event in patients with a nonsurgical fracture of a lower extremity immobilised in a below-knee plaster cast.

Description:

Study Design:

A prospective, randomised, controlled, single blinded, multi-centre trial.

Intervention:

After meeting the inclusion criteria stated above and obtaining informed consent, patients will be randomly assigned to three groups: one receiving Nadroparine (2850 IE anti-Xa = 0,3 ml, given once daily), one receiving Fondaparinux (2,5 mg = 0,5 ml, given once daily) and one receiving no prophylaxis. These dosages are standard for the use in thromboprophylaxis. The first two groups will be instructed by a trained nurse in subcutaneous self-injection of the medicine and will be given pre-filled disposable syringes for once-daily administration for the duration of immobilisation.

In the light of current scientific knowledge a placebo effect of subcutaneous injections of saline in the control group is implausible since the outcome measure (colour duplex sonography) is an objective one.

Patients further will receive a letter explaining the symptoms suggesting the development of deep-vein thrombosis, pulmonary embolism and adverse events and will be asked to contact the emergency room when any of these would occur.

All patient-information will be coded so that it cannot be traced back to the individual patient. This coded information can be used for publication.

Outcome:

At the time of removal of the plaster cast symptoms or signs suggestive of DVT will be noted and a colour duplex ultrasonography of the treated limb will be performed in all patients by an experienced technician according to a strict diagnostic test protocol (see enclosure 1). When there is incompressibility of a vein or lack of flow the diagnosis of DVT is made. The technician will be blinded to treatment.

In case of a suspected pulmonary embolism pulmonary angiography will be performed.

The following risk-factors for DVT will be recorded: age, sex, body mass index (BMI), current smoking, use of estrogen-containing hormonal replacement therapy or oral contraception, active cancer (treatment on going or stopped for less than one year), congenital or acquired hypercoagulable state, previous deep venous thromboembolism and varicose veins.

Safety will be assessed as a secondary outcome. Adverse events such as haematomas, bleeding and allergic reactions will be recorded.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 669
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• at least 18 years

• with a nonsurgical fracture of the lower extremity requiring immobilisation in a below-knee plaster cast for a minimum of 4 weeks.

Exclusion Criteria:

• Delay between injury and Emergency Department visit greater than three days

• Pregnancy/ lactation

• Body weight < 50 kg

• Severe hepatic impairment

• Severe renal impairment (creatinin-clearance < 30 ml/min)

• Known hypersensitivity to nadroparine or fondaparinux

• Pre-existing venous thromboembolism

• Pre-existing post-thrombotic syndrome

• Documented congenital or acquired bleeding tendency/disorder(s)

• Active, clinically significant bleeding

• Clinically significant bleeding within the past six months

• Previous or active bleeding from the digestive tract by peptic ulcer, tumours, hiatus hernia or diverticulosis

• Severe hypertension (systolic blood pressure above 180 mmHg or diastolic blood pressure above 110 mmHg)

• Bacterial endocarditis

• Haemorrhagic stroke within the previous two months

• Severe head injury within the previous three months

• Intraocular, spinal, and/or brain surgery within the previous twelve months

• Major surgery within the previous two months

• Treatment with LMWH or other anticoagulants

• Anticoagulant therapy required or likely to be required during the study period (e.g. planned surgery justifying pharmacological thromboprophylaxis)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Deep Vein Thrombosis
• Pulmonary Embolism
• Venous Thrombosis

Intervention

Drug:
• Nadroparin
nadroparin 0,3 cc once daily during immobilization period
• Fondaparinux
Fondaparinux 2,5 mg daily during immobilization period

Locations

Country	Name	City	State
Netherlands	Medical Center Alkmaar	Alkmaar	North Holland
Netherlands	VU University Medical Center	Amsterdam	N-Holland
Netherlands	Red Cross Hospital	Beverwijk	N-Holland
Netherlands	Spaarne Hospital	Hoofddorp	North Holland
Netherlands	University Medical Center Nijmegen	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Red Cross Hospital Beverwijk

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary outcome measure is deep vein trombosis as detected by venous duplex		subjects are assessed after 6 weeks	No
Secondary	Bleeding complications		6 weeks	Yes

External Links

•   study information