The API-CALF Study: Apixaban to Treat Calf Vein Thrombosis

NCT04981327 | Not Yet Recruiting Phase 3

• 1 other identifier: APICALF
• Study Type: interventional
• Target: 1,300
• Locations: 0 countries
• Sites: N/A

Brief Summary

Isolated distal DVT (iDDVT) is the most frequent clinical presentation of VTE and is associated with a significant morbidity and risks of long-term complications. Data from clinical trials highlighted that patients with iDDVT might require some level of AC treatment. However, the optimal anticoagulant intensity is uncertain, and it is plausible that the best benefit/risk ratio for AC might be achieved with lower intensity doses rather than therapeutic doses. The principal research question of the Apixaban to treat calf vein thrombosis (API-CALF) study is to determine whether, after a conventional course of 7 days of Apixaban 10mg BID, Apixaban 2.5mg BID (experimental arm) is non inferior to Apixaban 5 mg BID (standard arm) in preventing VTE recurrence and bleeding in patients with iDDVT. Patients will be treated with Apixaban for a total of 3 months. In that perspective we will conduct an international multicentre open-label assessor-blinded study

Conditions

Deep Vein Thrombosis

Keywords

Isolated distal deep vein thrombosis; Anticoagulation; Direct oral anticoagulants

Outcome Measures

Primary Outcomes (1)

• Rate of i) symptomatic VTE; ii) major bleeding and clinically relevant non major bleeding (CRNMB); iii) VTE and bleeding related death.

  The primary outcome is a composite of rate of i) symptomatic VTE (includes iDDVT involving a new distal deep vein, proximal DVT or PE; ii) major bleeding and clinically relevant non major bleeding (CRNMB); iii) VTE and bleeding related death.

  1 year

Secondary Outcomes (5)

• Individual components of the composite endpoint at 3 months and 1 year - Generic and venous disease-specific QOL scores at 1 year - Patient's compliance with treatment at 3 months - Serious adverse events during follow-up - PTS as measured at 1 year

  1 year

• Generic and venous disease-specific QOL scores at 1 year

  1 year

• Patient's observance with treatment at 3 months

  3 months

• Serious adverse events during follow-up

  1 year

• PTS as measured at 1 year

  1 year

Study Arms (2)

Experimental

EXPERIMENTAL

After a conventional course of 7 days of Apixaban 10mg BID, Apixaban 2.5mg BID during 3 months.

Drug: Apixaban 2.5 MG Oral Tablet [ELIQUIS]

Standard

ACTIVE COMPARATOR

After a conventional course of 7 days of Apixaban 10 mg BID, Apixaban 5 mg BID during 3 months.

Drug: Apixaban 2.5 MG Oral Tablet [ELIQUIS]

Interventions

Apixaban 2.5 MG Oral Tablet [ELIQUIS] DRUG

Apixaban 5 MG BID versus Apixaban 2.5 MG BID

Also known as: Apixaban 5 MG Oral Tablet

Experimental; Standard

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Age \< 18 years
• Ipsi or contralateral Proximal DVT
• Distal DVT involving the tibio-peroneal trunk (i.e. calf trifurcation)
• DVT occurring while on anticoagulation (started ≥48hours before DVT diagnosis); However, inpatients that developed their iDDVT while on prophylactic anticoagulation are eligible if their expected date of discharge is \<6 days post randomization.
• Clinically suspected PE (patient eligible if PE ruled out with objective tests)
• Active cancer, receiving cancer treatment or cured for \< 6 months
• Indication for long-term therapeutic anticoagulation (e.g. atrial fibrillation, mechanical heart valve…)
• Thrombocytopenia (platelet count \<100 g/l)
• Severe renal impairment (creatinine clearance \<30 ml/min)
• Liver disease (including Child-Pugh Class B and C) associated with coagulopathy
• Pregnant or breast-feeding woman
• Body weight \>120kg or \<40 kg
• Ongoing active bleeding or condition at high risk of bleeding with anticoagulation (e.g. peptic ulcer…)
• Treatment with daily NSAIDs (aspirin ≤160 mg/day or clopidogrel ≤75 mg day permitted)
• Allergy to Apixaban

Sponsors & Collaborators

• University Hospital, Geneva: lead
• Sunnybrook Health Sciences Centre: collaborator

Related Publications (31)

• Galanaud JP, Bosson JL, Quere I. Risk factors and early outcomes of patients with symptomatic distal vs. proximal deep-vein thrombosis. Curr Opin Pulm Med. 2011 Sep;17(5):387-91. doi: 10.1097/MCP.0b013e328349a9e3.

  PMID: 21832920 RESULT

• Schellong SM. Distal DVT: worth diagnosing? Yes. J Thromb Haemost. 2007 Jul;5 Suppl 1:51-4. doi: 10.1111/j.1538-7836.2007.02490.x.

  PMID: 17635708 RESULT

• 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.

  PMID: 27836513 RESULT

• Galanaud JP, Sevestre-Pietri MA, Bosson JL, Laroche JP, Righini M, Brisot D, Boge G, van Kien AK, Gattolliat O, Bettarel-Binon C, Gris JC, Genty C, Quere I; OPTIMEV-SFMV Investigators. Comparative study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: results from the OPTIMEV study. Thromb Haemost. 2009 Sep;102(3):493-500. doi: 10.1160/TH09-01-0053.

  PMID: 19718469 RESULT

• Johnson SA, Stevens SM, Woller SC, Lake E, Donadini M, Cheng J, Labarere J, Douketis JD. Risk of deep vein thrombosis following a single negative whole-leg compression ultrasound: a systematic review and meta-analysis. JAMA. 2010 Feb 3;303(5):438-45. doi: 10.1001/jama.2010.43.

  PMID: 20124539 RESULT

• Righini M, Bounameaux H. Clinical relevance of distal deep vein thrombosis. Curr Opin Pulm Med. 2008 Sep;14(5):408-13. doi: 10.1097/MCP.0b013e32830460ea.

  PMID: 18664970 RESULT

• Palareti G, Cosmi B, Lessiani G, Rodorigo G, Guazzaloca G, Brusi C, Valdre L, Conti E, Sartori M, Legnani C. Evolution of untreated calf deep-vein thrombosis in high risk symptomatic outpatients: the blind, prospective CALTHRO study. Thromb Haemost. 2010 Nov;104(5):1063-70. doi: 10.1160/TH10-06-0351. Epub 2010 Aug 5.

  PMID: 20694281 RESULT

• Bernardi E, Camporese G, Buller HR, Siragusa S, Imberti D, Berchio A, Ghirarduzzi A, Verlato F, Anastasio R, Prati C, Piccioli A, Pesavento R, Bova C, Maltempi P, Zanatta N, Cogo A, Cappelli R, Bucherini E, Cuppini S, Noventa F, Prandoni P; Erasmus Study Group. Serial 2-point ultrasonography plus D-dimer vs whole-leg color-coded Doppler ultrasonography for diagnosing suspected symptomatic deep vein thrombosis: a randomized controlled trial. JAMA. 2008 Oct 8;300(14):1653-9. doi: 10.1001/jama.300.14.1653.

  PMID: 18840838 RESULT

• Gibson NS, Schellong SM, Kheir DY, Beyer-Westendorf J, Gallus AS, McRae S, Schutgens RE, Piovella F, Gerdes VE, Buller HR. Safety and sensitivity of two ultrasound strategies in patients with clinically suspected deep venous thrombosis: a prospective management study. J Thromb Haemost. 2009 Dec;7(12):2035-41. doi: 10.1111/j.1538-7836.2009.03635.x. Epub 2009 Oct 8.

  PMID: 19817986 RESULT

• Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, Kearon C, Schunemann HJ, Crowther M, Pauker SG, Makdissi R, Guyatt GH. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e351S-e418S. doi: 10.1378/chest.11-2299.

  PMID: 22315267 RESULT

• Galanaud JP, Sevestre MA, Genty C, Pernod G, Quere I, Bosson JL. Is it useful to also image the asymptomatic leg in patients with suspected deep vein thrombosis?: comment. J Thromb Haemost. 2015 Nov;13(11):2127-30. doi: 10.1111/jth.13123. Epub 2015 Sep 30. No abstract available.

  PMID: 26332772 RESULT

• Palareti G. How I treat isolated distal deep vein thrombosis (IDDVT). Blood. 2014 Mar 20;123(12):1802-9. doi: 10.1182/blood-2013-10-512616. Epub 2014 Jan 28.

  PMID: 24472834 RESULT

• Palareti G, Schellong S. Isolated distal deep vein thrombosis: what we know and what we are doing. J Thromb Haemost. 2012 Jan;10(1):11-9. doi: 10.1111/j.1538-7836.2011.04564.x.

  PMID: 22082302 RESULT

• Righini M. Is it worth diagnosing and treating distal deep vein thrombosis? No. J Thromb Haemost. 2007 Jul;5 Suppl 1:55-9. doi: 10.1111/j.1538-7836.2007.02468.x.

  PMID: 17635709 RESULT

• Masuda EM, Kistner RL, Musikasinthorn C, Liquido F, Geling O, He Q. The controversy of managing calf vein thrombosis. J Vasc Surg. 2012 Feb;55(2):550-61. doi: 10.1016/j.jvs.2011.05.092. Epub 2011 Oct 26.

  PMID: 22032881 RESULT

• Lohr JM, Fellner AN. Isolated calf vein thrombosis should be treated with anticoagulation. Dis Mon. 2010 Oct;56(10):590-600. doi: 10.1016/j.disamonth.2010.06.010. No abstract available.

  PMID: 20971330 RESULT

• Masuda EM, Kistner RL. The case for managing calf vein thrombi with duplex surveillance and selective anticoagulation. Dis Mon. 2010 Oct;56(10):601-13. doi: 10.1016/j.disamonth.2010.06.011. No abstract available.

  PMID: 20971331 RESULT

• Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29;369(9):799-808. doi: 10.1056/NEJMoa1302507. Epub 2013 Jul 1.

  PMID: 23808982 RESULT

• Bauersachs RM, Herold J. Oral Anticoagulation in the Elderly and Frail. Hamostaseologie. 2020 Feb;40(1):74-83. doi: 10.1055/s-0040-1701476. Epub 2020 Jan 30.

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• Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. doi: 10.1056/NEJMoa1113697.

  PMID: 23425163 RESULT

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MeSH Terms

Conditions

Venous Thrombosis

Interventions

apixaban; Tablets

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Jean-Philippe Galanaud, MD, PhD

  Sunnybrook Health Sciences Centre and University of Toronto, Toronto, Canada

  PRINCIPAL INVESTIGATOR

• Marc Righini, MD

  Geneva University Hospital, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean-Philippe Galanaud, MD, PhD

CONTACT

001; Jean-Philippe.Galanaud@sunnybrook.ca

Marc Righini, MD

CONTACT

+41223729294; marc.righini@hcuge.ch

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Strategies to protect against bias include randomization with allocation concealment, enrolling consecutive patients. Patients will be advised to not disclose to study personnel during follow-up to which arm they were randomized to. Adjudicators will be blinded from treatment allocation group, and we will use standardized, validated measures to diagnose DVT, PE, PTS, and bleeding. We plan to allow phone follow-up to limit the risk of lost to follow-up and the impact on patients' in person consultation of a COVID wave during the course of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor

Study Record Dates

• First Submitted: July 7, 2021
• First Posted: July 29, 2021
• Study Start: September 1, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2027
• Last Updated: July 29, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share