Study of Apixaban in Patients Receiving Hemodiafiltration

NCT04952792 | Completed Phase 2 FDA Drug

• 1 other identifier: 2018-002991-41
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Atrial fibrillation (AF) is a prevalent and serious disease in hemodialysis (HD) patients. Untreated AF increases the risk of deaths related to cardiovascular events and multiplies the risk of strokes by 5. Anticoagulation with warfarin significantly reduces the incidence of ischemic strokes in the general population, has a long half-life, and a narrow therapeutic index that requires periodic monitoring. In addition, warfarin treatment is a frequent cause of hospital admission for iatrogenesis. In HD patients, the relationship between stroke prevention benefit and bleeding risk is an unmet medical need. It should be noted that in these patients the risk of bleeding is multiplied by 3 to 10 times compared to the general population. The new direct-acting oral anticoagulants (NACOs), thrombin inhibitors (dabigatran), and activated factor X inhibitors (rivaroxaban, apixaban, edoxaban), do not require regular monitoring, but their plasma concentrations are altered with the deterioration of the renal function. According to its technical data sheets, they do not recommend its use in clinical practice for HD patients. However, the apixaban data sheet includes the results of a pilot clinical trial in the African American population on HD, suggesting that it is a safe anticoagulant drug. The objective of this clinical trial is to evaluate the pharmacokinetics, pharmacodynamics, and short-term safety (4 weeks) of apixaban in the Spanish population with non-valvular atrial fibrillation and on hemodialysis. Long-term safety will be assessed in the extension study: prospective cohort study of patients included in the clinical trial. Therefore, this project is comprised of 2 clinical studies (one clinical trial and one extension study) whose objective is to evaluate the pharmacokinetics, pharmacodynamics, and short and long-term safety of apixaban in patients on hemodialysis and with non-valvular atrial fibrillation (FANV). The results of this project (clinical trial and extension study) will provide evidence on whether apixaban may be the anticoagulant treatment of choice for this type of patient.

Conditions

Atrial Fibrillation; Hemodialysis Complication

Outcome Measures

Primary Outcomes (1)

• Blood plasma concentrations of Apixaban before, during and after renal replacement therapy

  Determine the plasma concentrations of apixaban before, during and after renal replacement therapy (hemodialysis and hemodiafiltration)

  28 days

Secondary Outcomes (9)

• Urine plasma concentrations of Apixaban before, during and after renal replacement therapy

  28 days

• Anti-Factor Xa activity of apixaban (heparin activity (IU/mL))

  28 days

• Number of patients with medical complications with medical complications not directly related to the underlying disease.

  28 days

• Dyalisate concentrations of Apixaban before, during and after renal replacement therapy

  28 days

• Total number of adverse events.

  28 days

Study Arms (1)

Apixaban

EXPERIMENTAL

Apixaban treatment, oral, 2.5 mg/12h, 28 days

Drug: Apixaban 2.5 milligram Oral Tablet

Interventions

Apixaban 2.5 milligram Oral Tablet DRUG

Apixaban 2.5mg/12h, oral, 28 days

Apixaban

Eligibility Criteria

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

You may qualify if:

• Adults (18 years or older).
• Body weight ≥ 60 kg.
• Diagnosis of chronic kidney disease on hemodialysis, clinically stable (with a minimum of 3 months of treatment) and nonvalvular atrial fibrillation in treatment with coumarins.
• Patient candidate for change of anticoagulant treatment.
• In women of childbearing age, negative pregnancy test (negative human coriogonadotropine (hCG) urine test).
• The subject gives informed consent.

You may not qualify if:

• Pregnant or lactating women.
• Women of childbearing age (period of time from menarche to postmenopausal status, defined as 12 months absence of menstruation without other medical cause) who do not follow the contraceptive methods recommended by the Clinical Trial Facilitation Group (CTFG) (https://www.hma.eu/fileadm/dateien/Human\_Medicines/01): Hormonal contraceptives associated with ovulation inhibitors, intrauterine devices, surgical methods (tubal ligation, vasectomy), abstinence, and barrier methods.
• Body weight ≤ 60 kg.
• Presence of liver disease (patients with elevated liver enzyme levels alanine aminotransferase (ALT) / aspartate aminotransferase (AST)\> 2x the upper limit of normal, or total bilirubin\> 1.5 ULN).
• Thrombopenia (\<100.000 platelets/mL).
• Be on treatment with other anticoagulants (heparins) or antiplatelet drugs.
• Be treated with enzyme inhibitors (such as azole antifungals or HIV protease inhibitors) or enzyme inducers (such as rifampin, phenobarbital, carbamazepine, or phenytoin) of CYP3A4 (Cytochrome P450 3A4 oxidase ).
• History of bleeding episode in the last month.
• Presence of clinical or analytical alterations not attributable to the stage of kidney disease
• Participation in another clinical trial of pharmacological treatment.

Sponsors & Collaborators

• Hospital Universitari de Bellvitge: lead
• Spanish Society of Nephrology: collaborator
• Baxter Healthcare Corporation: collaborator

Study Sites (1)

Carolina Polo

Barcelona, 08907, Spain

Location

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: July 7, 2021
• Study Start: May 20, 2021
• Primary Completion: December 15, 2022
• Study Completion: December 15, 2022
• Last Updated: September 21, 2023

Record last verified: 2023-09

Locations

ES (1)