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

Prevention of Dialysis-Induced Hypotension by Inhibiting Plasma Kallikrein

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

Study Overview

• Status: Active, not recruiting
• Conditions: Hemodialysis Complication; Hypotension of Hemodialysis
• Intervention / Treatment: Drug: Placebo; Drug: Lanadelumab Injection [Takhzyro]

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lanadelumab; Subjects will receive lanadelumab (300 mg) subcutaneously at the beginning of the study and 14 days later	Drug: Lanadelumab Injection [Takhzyro]; Lanadelumab 300 mg subcutaneous injection
Placebo Comparator: Placebo; Subjects will receive placebo subcutaneously at the beginning of the study and 14 days later	Drug: Placebo; Placebo injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure During Hemodialysis	Systolic blood pressure pre and post hemodialysis at baseline and at the end of the study	From the initiation of study until the end (week 6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypotensive Episodes	Number of hypotensive episodes during hemodialysis after the second week of treatment	From the second week of the study until the end (week 6)

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2022
• Primary Completion (Actual): December 30, 2024
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: March 17, 2022
• First Submitted That Met QC Criteria: March 17, 2022
• First Posted (Actual): March 28, 2022

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: December 30, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypotension; lanadelumab
• Other Study ID Numbers: 210633

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No