Reduction of Plasma Free VEGF-A Using Low-dose Bevacizumab in Hemodialysis Patients

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Clinical Phase

EARLY_PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-01

Study Completion Date

2021-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The primary purpose of this pilot study is to assess the pharmacokinetic profile of low-dose bevacizumab and its effectiveness in reducing plasma free VEGF-A levels safely in hemodialysis patients. This information will be used to plan a phase 1 clinical trial evaluating bevacizumab's role in hemodialysis vascular access failure.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Trial Comparing Angiography and Angiography With IVUS for Treatment of Hemodialysis Access Failures

NCT02056704

Dialysis Access Malfunction

COMPLETED PHASE4

Oral Anticoagulation in Haemodialysis Patients

NCT02886962

Kidney Failure, Chronic

TERMINATED PHASE4

Reduction of Heparin Dose in Dialysis With Evodial System

NCT00781690

Chronic Kidney Failure

COMPLETED NA

Heparin Free Haemodialysis With Haemodialyzers "VIE" Versus "EVODIAL"

NCT01221337

Adult Chronic Haemodialysis Patients Since at Least 3 Months

COMPLETED NA

Development of an Innovative Hemodialysis Method to Improve Dialytic Clearance of Protein-bound Uremic Toxins

NCT06595680

End Stage Renal Disease Chronic Hemolysis

NOT_YET_RECRUITING PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

It has been found that hemodialysis arteriovenous fistula failure is partly mediated through a VEGF pathway. The administration of bevacizumab (a VEGF-A monoclonal antibody) in arteriovenous fistula (AVF) murine models at a dose of 5mg/kg (a standard chemotherapeutic dose) has shown a significant reduction in stenosis formation and an overall improvement in vascular remolding. However, previous pharmacokinetic human studies have shown that bevacizumab administered at a low dose of 1.25mg intravitreally (ocular neovascularization patients) is sufficient enough to suppress circulating VEGF-A levels up to 30 days post administration. A chart review on 14 hemodialysis patients receiving an arteriovenous access and intravitreal bevacizumab has demonstrated a significant improvement in patency (HR: 0.45, p-value: 0.037) when compared to controls. Prior to a phase 1 trial, it is essential to determine if intravenous administration of bevacizumab demonstrates the same pharmacokinetics and bio-response profile as intravitreal administration, and to determine the optimal dose and frequency. This phase 0 study will be conducted in 10 existing hemodialysis patients at a dose of 1.25mg with a potential dose escalation to 2.5mg if optimal results are not seen. The findings from this study can have a substantial clinical impact not only in ESRD patients but also in patients receiving other vascular or endovascular procedures.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

End Stage Renal Disease Hemodialysis Vascular Access Failure

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

SINGLE

Participants

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Stage 1 - Low dose administration

Ten hemodialysis patients will receive IV infusion treatment with 1.25mg bevacizumab and undergo serial blood draws on Days 0, 1, 3, 6, 10, 15, 22, and 29 during dialysis sessions. ELISA will be performed to evaluate drug serum concentration and corresponding plasma free VEGF-A levels (pg/ml). The safety and pharmacokinetic/dynamic (PK/PD) data will be analysed and ≥50% VEGF-A suppression retained from baseline by Day 15 will be considered successful. If target outcomes are met in stage 1, the study will be terminated, otherwise the study will progress to stage 2.

Group Type EXPERIMENTAL

1.25mg bevacizumab

Intervention Type DRUG

Bevacizumab is a monoclonal antibody against VEGF-A. 1.25mg in 50ml 0.9% Sodium Chloride will be administered once as an intravenous infusion over 30 minutes.

Stage 2 - Dose escalation

If outcomes are not met in stage 1, Ten additional hemodialysis patients will receive IV infusion treatment with 2.50mg bevacizumab treatment. They will undergo serial blood draws on Days 0, 1, 3, 6, 10, 15, 22, and 29 during dialysis sessions. ELISA will be performed to evaluate drug serum concentration and corresponding plasma free VEGF-A levels (pg/ml). The safety and PK/PD data will be analysed and ≥50% VEGF-A suppression retained from baseline by Day 15 will be considered successful. If target outcome is not met, the study will be terminated.

Group Type EXPERIMENTAL

2.50mg bevacizumab

Intervention Type DRUG

Bevacizumab is a monoclonal antibody against VEGF-A. 2.50mg in 50ml 0.9% Sodium Chloride will be administered once as an intravenous infusion over 30 minutes.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

1.25mg bevacizumab

Bevacizumab is a monoclonal antibody against VEGF-A. 1.25mg in 50ml 0.9% Sodium Chloride will be administered once as an intravenous infusion over 30 minutes.

Intervention Type DRUG

2.50mg bevacizumab

Bevacizumab is a monoclonal antibody against VEGF-A. 2.50mg in 50ml 0.9% Sodium Chloride will be administered once as an intravenous infusion over 30 minutes.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Avastin Avastin

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients between 18 and 85 years old, inclusive
* Patients with end stage renal disease (ESRD) who are currently undergoing hemodialysis treatment through an upper extremity fistula
* Hemoglobin ≥8g/dL and platelet count ≥100,000/mm3 prior to Day 1
* Adequate liver function, defined as serum bilirubin ≤1.5 mg/dL; gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase ≤2x upper limit of normal or international normalized ratio (INR) ≤ 1.5 prior to Day 0 or INR ≤ 2 if on anticoagulant therapy.
* Ability to communicate meaningfully with investigative staff, competence to give written informed consent, and ability to comply with entire study procedures
* If female and of childbearing years, must have a negative serum pregnancy test at the screening visit (Visit 1). Both female patients of childbearing potential and male patients with childbearing potential partners must be willing to use contraception from the time of screening to completion of the study
* Life expectancy of at least 1 year

Exclusion Criteria

* Known sensitivity to bevacizumab or prior treatment with any medication known to target VEGF
* Current use of medications that are known to interact with the safety and efficacy of bevacizumab (most commonly: Antineoplastics (Anthracyclines), Belimumab, Bisphosphonate Derivatives, Clozapine, Dipyrone, Irinotecan, Sorafenib, and Sutent)
* History or evidence of severe cardiac disease (NYHA Functional Class III or IV), myocardial infarction within six months of study entry (Day 1), ventricular tachyarrhythmias requiring continuing treatment, or unstable angina
* Significant uncontrolled hypertension (systolic blood pressure above 160 mm Hg and/or diastolic blood pressure above 100 mm Hg);
* Stroke within six (6) months of study entry (Day 1)
* Treatment with any investigational drug/ device within 60 days prior to study entry (Day1)
* Treatment with vitamin K-antagonists or direct thrombin inhibitors with an INR ≥2
* All patients (including both female patients of childbearing potential and male patients with childbearing potential partners) who do not use a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly), e.g. implants, injectables, combined oral contraceptives in combination with a barrier method, some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner
* Malignancy or treatment for malignancy within the previous 6 months
* Immunodeficiency including AIDS / HIV or Active autoimmune disease
* Documented hypercoagulable state or history of 2 or more deep vein thromboses (DVTs) or other spontaneous intravascular thrombotic events
* Bleeding diathesis or Anemia with a hematocrit level of less than 30%
* A prothrombin time or a partial thromboplastin time more than 1.2 times the upper limit of normal, or absolute platelet counts below the lower limit of normal; an absolute neutrophil count below 1,500/mm3
* Active local or systemic infection (WBC \> 15,000/mm3)
* Gastrointestinal ulcer or bleeding, or wound dehiscence
* Scheduled elective surgery within 2 months of start date
* Known serious allergy to aspirin or penicillin
* Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of bevacizumab
* Employees of the sponsor or patients who are employees or relatives of the investigator

Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No