Management of Atrial Fibrillation in Patients With Cancer (MAFIC Study) (MAFIC)

February 14, 2022 updated by: Thomas Zegkos, AHEPA University Hospital

Safety and Efficacy of Switching From Direct Oral Anticoagulants to Low Molecular Weight Heparin in Cancer Patients With Atrial Fibrillation During Antineoplastic Therapy

The primary objective is to assess the safety and efficacy of switching from direct oral anticoagulants to low molecular weight heparin in cancer patients during antineoplastic therapy

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a single-arm prospective observational study aiming to explore the safety and efficacy of switching from direct oral anticoagulants (DOAC) to low molecular weight heparin (LMWH) in cancer patients with atrial fibrillation (AF) during antineoplastic therapy or for a maximum time period of 6 months.

AF is the most common sustained arrhythmia; it affects 1.5% to 2% of the general population, and this prevalence increases to 10% at 80 years of age and to 18% at 85 years of age. Given the increasing occurrence of malignancies in the elderly and the coexistence of other conditions predisposing to AF in cancer patients, an association between those 2 conditions would be expected. A study including 24,125 patients estimated a prevalence of AF of 2.4% at the time of cancer diagnosis. A recent prospective study of 34,691 middle-aged women without AF or cancer at baseline showed that new-onset AF was a risk marker of subsequent diagnosis of cancer (HR 1.48, 95% CI 1.25 to 1.75; p <0.001).

Moreover, patients with cancer are at significantly higher risk of developing venous thromboembolism (VTE) which sometimes may precede the diagnosis of the malignancy. The risk is even higher when the patient is poorly mobilized or hospitalized. On the other hand, some anticancer therapies and especially the novel angiogenesis inhibitors are associated with increased thrombogenicity.

According to current Guidelines, DOACs are preferred over vitamin K antagonist (VKA) therapy and LMWH in both AF and VTE in the general population. However, in the presence of active cancer the administration of LMWH is advised for patients who are hospitalized for any reason and/or receiving chemotherapy, unless there is a high bleeding risk. LMWH has more favorable outcomes in cancer patients than VKAs, both in the setting of primary or secondary thromboembolic prophylaxis while extended anticoagulation (beyond the first 6 months) may be considered for an indefinite period or until the cancer is cured. This is possibly related with the fact that LMWH present antitumour and antimetastatic effects and confer an increased survival benefit. It should be noted that currently there is no conclusive evidence regarding the safety and efficacy of DOACs in cancer patients and the first results seem contradictory.

A number of recent studies with the use of DOACs in cancer-associated venous thromboembolism have demonstrated that these drugs are effective with similar rates of recurrent VTE but higher rates of major bleeding compared to LMWH. However, there are particular disadvantages, especially during the period of chemotherapy, such as interactions between these agents and anticancer therapies (eg, potential interactions between DOACs and azole-antimycotic agents), as well as unknown pharmacokinetics from chemotherapy-related vomiting.

Putting things together, many patients who are under a DOAC due to AF or previous VTE/pulmonary embolism (PE) may be diagnosed with cancer. Moreover, the risk of VTE is 6-fold higher on intravenous chemotherapy. For this reason, current clinical practice suggests that LMWH is continued during treatment with intravenous chemotherapy. However, data on the efficacy and safety of this common approach is lacking. This is important, especially in the setting of gastrointestinal tumors (especially gastric and pancreatic disease) which pose a high bleeding risk and especially during the chemotherapy active period.

Study Type

Observational

Enrollment (Anticipated)

240

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Greece
      • Thessaloniki, Greece, 54636
        • Recruiting
        • Ahepa University Hospital
        • Contact:
        • Principal Investigator:
          • Georgios Giannakoulas, MD
        • Sub-Investigator:
          • Thomas Zegkos, MD
        • Sub-Investigator:
          • Eleni Hamalidou, MD
      • Thessaloniki, Greece
        • Recruiting
        • Theagenio Cancer Hospital
        • Contact:
          • Pavlos Papakotoulas, MD
        • Principal Investigator:
          • Pavlos Papakotoulas, MD
        • Principal Investigator:
          • Ioannis Lafaras, MD
        • Principal Investigator:
          • Theodoros Mpisxiniotis, MD
        • Principal Investigator:
          • Alexandros Mpokas, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

All patients with cancer and atrial fibrillation receiving direct oral anticoagulants and antineoplastic therapy

Description

Inclusion Criteria:

  1. Subjects diagnosed with cancer other than basal-cell or squamous-cell skin cancer which was objectively confirmed and are programmed for antineoplastic treatment
  2. Subjects between 18 to 75 years of age at inclusion
  3. Subjects must weigh at least 40 kg at inclusion
  4. Subjects receiving direct oral anticoagulant treatment (rivaroxaban, dabigatran, apixaban, edoxaban) for prevention of stroke and systemic embolism in non-valvular atrial fibrillation

Exclusion Criteria:

  1. Patients that have active or serious bleeding within the previous two weeks
  2. Patients that have conditions associated with high bleeding risk (active peptic ulcer, recent neurosurgery
  3. Patients with platelet count below 50000 per cubic millimeter
  4. Patients who have contraindications to heparin (heparin-induced thrombocytopenia)
  5. Patients with calculated creatinine clearance < 30 ml/min using the Cockcroft-Gault formula
  6. Women who are pregnant
  7. Life expectancy less than 6 months
  8. Anticoagulation contraindications
  9. Recent brain surgery within 6 months
  10. Vascular surgery within 6 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cancer patients with atrial fibrillation

All patients will be assigned to receive subcutaneous LMWH in therapeutic doses

More specifically the regimens will be as follows:

Tinzaparin 175 units/Kg once daily; Enoxaparin 1unit/kg twice daily; Fondaparinux <50 kg, 5 mg SC once daily, 50-100 kg, 7.5 mg SC once daily, >100 kg, 10 mg SC once daily; Bemiparin 115 IU/kg once daily; <50kg, 5000IU, 50-70kg, 7.500 IU, >70kg, 10000IU Nadroparin: Patients weighing 40 to 100 kg: SC, 171 anti-factor Xa IU per kg of body weight once a day; patients weighing over 100 kg will not receive nadroparin because a treatment dosage has not been established; Dalteparin: 200 units IU/kg SC daily for 30 days, then 150 units IU/Kg SC daily Dose adjustments will occur only in case of renal insufficiency according to the medicine's SPC The treatment with the LMWH will last at least during the period of active antineoplastic therapy of cancer patients
Drug: Low molecular weight heparin
Switch from direct oral anticoagulants to low molecular weight heparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major bleeding
Time Frame: 6 months
Death or a decrease in hemoglobin level of ≥ 2 g/dL over 24 hours or the need for transfusion of ≥ 2 units of packed red cells or clinically overt bleeding at critical site (eg, intracranial, retroperitoneal)
6 months
Clinical relevant bleeding
Time Frame: 6 months
Bleeding that does not meet the criteria for major bleeding, however, it requires medical treatment or it affects the patient's daily activity
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Deep vein thrombosis or pulmonary embolism
Time Frame: 6 months
t The first episode of symptomatic, documented deep vein thrombosis or pulmonary embolism
6 months
Thromboembolic stroke or systemic embolism
Time Frame: 6 months
The first episode of symptomatic, documented thromboembolic stroke or systemic embolism
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AHEPA University Hospital

Collaborators

Theagenio Cancer Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 1, 2020

Primary Completion (ANTICIPATED)

August 1, 2023

Study Completion (ANTICIPATED)

December 1, 2023

Study Registration Dates

First Submitted

August 8, 2020

First Submitted That Met QC Criteria

August 8, 2020

First Posted (ACTUAL)

August 11, 2020

Study Record Updates

Last Update Posted (ACTUAL)

February 15, 2022

Last Update Submitted That Met QC Criteria

February 14, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MAFIC_2020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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