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Randomized Controlled Trial of Anticoagulation vs. Placebo for a First Symptomatic Isolated Distal Deep-vein Thrombosis (IDDVT) (CACTUS-PTS)

Primary Purpose

Distal (Calf) Deep-vein Thrombosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
nadroparine calcium
Placebo
Sponsored by
University Hospital, Geneva
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Distal (Calf) Deep-vein Thrombosis focused on measuring Deep vein Thrombosis, Calf vein thrombosis, Low-molecular weight heparin, Placebo, Elastic contention, Compression Ultrasonography

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • All outpatients with an acute, symptomatic, distal DVT will be included in the study, provided they correspond to the following diagnostic and exclusion criteria, and they have signed an informed consent form.

Exclusion Criteria:

  • Age less than 18 years
  • Previously objectively diagnosed DVT or PE
  • Distal DVT involving the tibioperoneal trunk (i.e. calf trifurcation)
  • Clinically suspected pulmonary embolism
  • Active cancer, receiving cancer treatment or cancer considered cured for <6 months
  • Ipsilateral or contralateral proximal DVT
  • Indication for long-term anticoagulation (e.g. atrial fibrillation, mechanical heart valve...)
  • Pregnancy
  • Thrombocytopenia (platelet count < 100 g/l)
  • Impaired renal function (serum creatinine > 180 micromol/l or clearance to creatinine less than 30 ml/min)
  • Known hypersensitivity to heparin
  • Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (gastric ulcer, cerebral malignant disease...)
  • Treatment with daily NSAIDs (aspirin ≤160 mg/day permitted)
  • Body weight >115 kg or <40 kg
  • Treatment with therapeutic doses of anticoagulants for >2 days, corresponding to: 2 injections of LMWH if once daily therapeutic LMWH used; 3 injections of LMWH if twice-daily therapeutic LMWH used; 1 dose of oral vitamin K antagonist (e.g. warfarin)
  • Ongoing requirement for prophylactic dose thromboprophylaxis (e.g. acute post-op patient receiving thromboprophylaxis)
  • Enrolled in another clinical trial within previous 30 days
  • Inability or refusal to provide informed consent

Sites / Locations

  • Hamilton General Hospital
  • Ottawa General Hospital
  • Hopital Maisonneuve-Rosemont
  • Jewish General Hospital
  • Royal University Hospital
  • Montpellier University Hospital
  • University Hospital of Geneva

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

LMWH

Placebo

Arm Description

Therapeutic dose of Nadroparin

Injectable placebo

Outcomes

Primary Outcome Measures

Composite of rate of extension of distal DVT to proximal deep veins (includes ipsilateral extension or new contralateral proximal DVT) or symptomatic PE at 6 weeks
Rate of post-thrombotic syndrome (PTS)
Rate of post-thrombotic syndrome (PTS) diagnosed using the Villalta scale.

Secondary Outcome Measures

Individual components of the composite endpoint: distal DVT extension to proximal veins at 6 weeks and 90 days; PE at 6 weeks and 90 days
Major bleeding at 6 weeks and 90 days
Death at 6 weeks and 90 days
Serious adverse events at 6 weeks and 90 days
Generic and venous disease-specific Quality of Life scores
PTS severity category
Can either be mild, intermediate, severe

Full Information

First Posted
January 11, 2007
Last Updated
May 3, 2018
Sponsor
University Hospital, Geneva
Collaborators
Swiss National Science Foundation, Ministry of Health, France, Lady Davis Institute, Canadian Institutes of Health Research (CIHR)
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1. Study Identification

Unique Protocol Identification Number
NCT00421538
Brief Title
Randomized Controlled Trial of Anticoagulation vs. Placebo for a First Symptomatic Isolated Distal Deep-vein Thrombosis (IDDVT)
Acronym
CACTUS-PTS
Official Title
Contention Alone Versus Anticoagulation for Symptomatic Calf Vein Thrombosis Diagnosed by Ultrasonography
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
January 2008 (Actual)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Geneva
Collaborators
Swiss National Science Foundation, Ministry of Health, France, Lady Davis Institute, Canadian Institutes of Health Research (CIHR)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
CACTUS-PTS is a randomized, placebo-controlled, double-blind study which aims primarily to determine the effectiveness of a 6 week course of therapeutic-dose LMWH (nadroparine) injections vs. placebo in patients with a first symptomatic isolated distal (calf) deep-vein thrombosis (IDDVT), as measured by rate of proximal DVT and symptomatic PE at 6 weeks. Additionally, the study aims to determine if the 6 week course of treatment with therapeutic-dose LMWH (nadroparine) injections, compared to placebo, decreases the frequency of post-thrombotic syndrome (PTS) at 1 year.
Detailed Description
The CACTUS-PTS study will compare anticoagulant treatment for 6 weeks versus placebo in acute, symptomatic distal DVT. Patients will be randomized to receive either a six-week period of LMWH at therapeutic dosage or a six-week period of placebo. All patients will be treated with elastic compression stockings and followed-up with a standardized ultrasonography protocol. Strict ultrasonographic diagnostic criteria for distal DVT have been defined. Control compression ultrasonography will be performed between days 3 and 7 and at six weeks after inclusion. The primary outcome will be a composite of the proportion of patients with extension of the thrombus to the proximal veins (detected by the programmed ultrasound examinations or by an ultrasound performed because of recurrent symptoms) or symptomatic PE in both arms of the study during the 6-weeks study period. Patients with such an outcome will be anticoagulated as currently admitted in presence of a proximal DVT. Secondary outcomes will be the individual components of the composite endpoint (distal DVT extension to proximal veins; symptomatic PE), major bleeding, serious adverse events and death reported at 6 weeks and 90 days. To answer the research question of the PTS add-on study, patients will self-assess and be assessed for PTS by a clinician using the Villalta scale, 1 year following their enrolment into the trial. In addition, patients will complete a Quality of Life (QOL) questionnaire. The QOL questionnaire will be comprised of both the VEINES-QOL and SF-36. The primary outcome is the rate of PTS, with secondary outcomes of QOL scores and PTS severity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Distal (Calf) Deep-vein Thrombosis
Keywords
Deep vein Thrombosis, Calf vein thrombosis, Low-molecular weight heparin, Placebo, Elastic contention, Compression Ultrasonography

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
260 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LMWH
Arm Type
Active Comparator
Arm Description
Therapeutic dose of Nadroparin
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Injectable placebo
Intervention Type
Drug
Intervention Name(s)
nadroparine calcium
Intervention Description
Once-daily injection of 171 U/Kg/day of nadroparine calcium for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Once-daily injectable placebo (sterilized NaCL 0.9%) for 6 weeks
Primary Outcome Measure Information:
Title
Composite of rate of extension of distal DVT to proximal deep veins (includes ipsilateral extension or new contralateral proximal DVT) or symptomatic PE at 6 weeks
Time Frame
6 weeks
Title
Rate of post-thrombotic syndrome (PTS)
Description
Rate of post-thrombotic syndrome (PTS) diagnosed using the Villalta scale.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Individual components of the composite endpoint: distal DVT extension to proximal veins at 6 weeks and 90 days; PE at 6 weeks and 90 days
Time Frame
6 weeks and 3 months
Title
Major bleeding at 6 weeks and 90 days
Time Frame
6 weeks and 3 months
Title
Death at 6 weeks and 90 days
Time Frame
6 weeks and 3 months
Title
Serious adverse events at 6 weeks and 90 days
Time Frame
6 weeks and 3 months
Title
Generic and venous disease-specific Quality of Life scores
Time Frame
1 year
Title
PTS severity category
Description
Can either be mild, intermediate, severe
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All outpatients with an acute, symptomatic, distal DVT will be included in the study, provided they correspond to the following diagnostic and exclusion criteria, and they have signed an informed consent form. Exclusion Criteria: Age less than 18 years Previously objectively diagnosed DVT or PE Distal DVT involving the tibioperoneal trunk (i.e. calf trifurcation) Clinically suspected pulmonary embolism Active cancer, receiving cancer treatment or cancer considered cured for <6 months Ipsilateral or contralateral proximal DVT Indication for long-term anticoagulation (e.g. atrial fibrillation, mechanical heart valve...) Pregnancy Thrombocytopenia (platelet count < 100 g/l) Impaired renal function (serum creatinine > 180 micromol/l or clearance to creatinine less than 30 ml/min) Known hypersensitivity to heparin Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (gastric ulcer, cerebral malignant disease...) Treatment with daily NSAIDs (aspirin ≤160 mg/day permitted) Body weight >115 kg or <40 kg Treatment with therapeutic doses of anticoagulants for >2 days, corresponding to: 2 injections of LMWH if once daily therapeutic LMWH used; 3 injections of LMWH if twice-daily therapeutic LMWH used; 1 dose of oral vitamin K antagonist (e.g. warfarin) Ongoing requirement for prophylactic dose thromboprophylaxis (e.g. acute post-op patient receiving thromboprophylaxis) Enrolled in another clinical trial within previous 30 days Inability or refusal to provide informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Righini, MD
Organizational Affiliation
University Hospital, Geneva
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Isabelle Quéré, MD
Organizational Affiliation
Montpellier University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Susan Kahn, MD
Organizational Affiliation
Jewish General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marc Carrier, MD
Organizational Affiliation
Ottawa Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hamilton General Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 2X2
Country
Canada
Facility Name
Ottawa General Hospital
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
Hopital Maisonneuve-Rosemont
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Royal University Hospital
City
Saskatoon
State/Province
Saskatchewan
Country
Canada
Facility Name
Montpellier University Hospital
City
Montpellier
State/Province
Languedoc
ZIP/Postal Code
34295
Country
France
Facility Name
University Hospital of Geneva
City
Geneva
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
30656824
Citation
Righini M, Robert-Ebadi H, Glauser F, Blondon M, Ouvry P, Diamand JM, Tissot A, Frappe P, Quere I, Kahn SR, Galanaud JP, Le Gal G. Effect of anticoagulant treatment on pain in distal deep vein thrombosis: an ancillary analysis from the cactus trial. J Thromb Haemost. 2019 Mar;17(3):507-510. doi: 10.1111/jth.14387. Epub 2019 Feb 3.
Results Reference
derived
PubMed Identifier
27836513
Citation
Righini M, Galanaud JP, Guenneguez H, Brisot D, Diard A, Faisse P, Barrellier MT, Hamel-Desnos C, Jurus C, Pichot O, Martin M, Mazzolai L, Choquenet C, Accassat S, Robert-Ebadi H, Carrier M, Le Gal G, Mermilllod B, Laroche JP, Bounameaux H, Perrier A, Kahn SR, Quere I. Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial. Lancet Haematol. 2016 Dec;3(12):e556-e562. doi: 10.1016/S2352-3026(16)30131-4. Epub 2016 Nov 8.
Results Reference
derived
PubMed Identifier
22648486
Citation
Guanella R, Righini M. Serial limited versus single complete compression ultrasonography for the diagnosis of lower extremity deep vein thrombosis. Semin Respir Crit Care Med. 2012 Apr;33(2):144-50. doi: 10.1055/s-0032-1311793. Epub 2012 May 30.
Results Reference
derived

Learn more about this trial

Randomized Controlled Trial of Anticoagulation vs. Placebo for a First Symptomatic Isolated Distal Deep-vein Thrombosis (IDDVT)

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