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

NCT ID: NCT00421538

Last Updated: 2018-05-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2015-08-31

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.

Conditions

Distal (Calf) Deep-vein Thrombosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

LMWH

Therapeutic dose of Nadroparin

Group Type: ACTIVE_COMPARATOR

nadroparine calcium

Intervention Type: DRUG

Once-daily injection of 171 U/Kg/day of nadroparine calcium for 6 weeks.

Placebo

Injectable placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Once-daily injectable placebo (sterilized NaCL 0.9%) for 6 weeks

Interventions

nadroparine calcium

Once-daily injection of 171 U/Kg/day of nadroparine calcium for 6 weeks.

Intervention Type: DRUG

Placebo

Once-daily injectable placebo (sterilized NaCL 0.9%) for 6 weeks

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss National Science Foundation

OTHER

Sponsor Role: collaborator

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

Lady Davis Institute

OTHER

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Geneva

OTHER

Sponsor Role: lead

Responsible Party

Marc Righini

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marc Righini, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Geneva

Isabelle Quéré, MD

Role: PRINCIPAL_INVESTIGATOR

Montpellier University Hospital

Susan Kahn, MD

Role: PRINCIPAL_INVESTIGATOR

Jewish General Hospital

Marc Carrier, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital

Locations

Hamilton General Hospital

Hamilton, Ontario, Canada

Ottawa General Hospital

Ottawa, Ontario, Canada

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Jewish General Hospital

Montreal, Quebec, Canada

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Montpellier University Hospital

Montpellier, Languedoc, France

University Hospital of Geneva

Geneva, , Switzerland

Countries

Canada; France; Switzerland

References

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.

Reference Type: DERIVED

PMID: 30656824 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27836513 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22648486 (View on PubMed)

Other Identifiers

CACTUS-PTS Trial

Identifier Type: -

Identifier Source: secondary_id

3200B0-105991

Identifier Type: -

Identifier Source: org_study_id

NCT00539058

Identifier Type: -

Identifier Source: nct_alias