Hemodialysis.-Induced Hypotension Therapy for End Stage Kidney Disease (Hinder)

Vanderbilt University Medical Center

Status and phase: Active, not recruiting; Phase 2

Conditions: Hemodialysis Complication; Hypotension of Hemodialysis

Treatments: Drug: Lanadelumab Injection [Takhzyro]; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05297786

210633

Details and patient eligibility

About

Bradykinin is a potent vasodilator that is formed by the activation of the kallikrein-kinin system. We and others have shown that bradykinin increased during hemodialysis; however, the role of bradykinin in dialysis-induced hypotension (DIH) has not been evaluated. Preliminary results from a pilot clinical trial showed that bradykinin B2 receptor blockade with icatibant prevents excessive blood pressure during hemodialysis. Thus, in this study, we will test the overarching hypothesis that blockade plasma kallikrein with lanadelumab would ameliorate the reduction of blood pressure during hemodialysis in patients who are prone to DIH. For this purpose, we will conduct a parallel arm, double-blind placebo-controlled trial, using lanadelumab to evaluate the occurrence of

Enrollment: 28 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects age 18 to 85 years
• On thrice-weekly hemodialysis for at least six months
• Clinically stable, adequately dialyzed (single-pool Kt/V > 1.2), with polysulphone membrane for at least three consecutive months before the study
• Subjects with pre-dialytic systolic blood pressure between 110 and 170 mmHg.
• Subjects with a reduction of systolic blood pressure during hemodialysis equal to or greater than 30 mmHg, with associated symptoms such as nausea, vomiting, muscle cramps, dizziness, or anxiety.
• Hypotensive episodes should occur four times or more in four weeks (12 hemodialysis sessions).

Exclusion criteria

• Subjects with intradialytic hypotension that require the use of pharmacological intervention such as midodrine or vasopressin
• Subjects with pre-dialytic systolic blood pressure greater than 170 mmHg or diastolic blood pressure greater than 110 mmHg
• History of myocardial infarction or cerebrovascular event within 3 months
• History of serious hemorrhage (including cerebral hemorrhage) in the past 6 months
• Advanced liver disease
• Ejection fraction less than 30%
• Anticipated live donor kidney transplant
• A history of poor adherence to hemodialysis or medical regimen
• Severe anemia (hemoglobin less than 8 g/dl) requiring blood transfusions
• Use of immunosuppressive drugs within one month before study enrollment
• Active connective tissue disease
• History of acute infections disease within one month before study enrollment
• Inability to provide consent
• Pregnancy

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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28 participants in 2 patient groups, including a placebo group

Lanadelumab

Experimental group

Description:

Subjects will receive lanadelumab (300 mg) subcutaneously at the beginning of the study and 14 days later

Treatment:

Drug: Lanadelumab Injection [Takhzyro]

Placebo

Placebo Comparator group

Description:

Subjects will receive placebo subcutaneously at the beginning of the study and 14 days later

Treatment:

Drug: Placebo