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

Primary Purpose

Hemodialysis Complication, Hypotension of Hemodialysis

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Lanadelumab Injection [Takhzyro]
Placebo
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hemodialysis Complication

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Vanderbilt University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Lanadelumab

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Blood Pressure during hemodialysis
Average blood pressure during hemodialysis of three hemodialysis sessions after the second week of treatment.

Secondary Outcome Measures

Hypotensive episodes
Number of hypotensive episodes during hemodialysis after the second week of treatment

Full Information

First Posted
March 17, 2022
Last Updated
August 15, 2023
Sponsor
Vanderbilt University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05297786
Brief Title
Hemodialysis.-Induced Hypotension Therapy for End Stage Kidney Disease
Acronym
Hinder
Official Title
Prevention of Dialysis-Induced Hypotension by Inhibiting Plasma Kallikrein
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 27, 2022 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemodialysis Complication, Hypotension of Hemodialysis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Lanadelumab
Arm Type
Experimental
Arm Description
Subjects will receive lanadelumab (300 mg) subcutaneously at the beginning of the study and 14 days later
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will receive placebo subcutaneously at the beginning of the study and 14 days later
Intervention Type
Drug
Intervention Name(s)
Lanadelumab Injection [Takhzyro]
Intervention Description
Lanadelumab 300 mg subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo injection
Primary Outcome Measure Information:
Title
Blood Pressure during hemodialysis
Description
Average blood pressure during hemodialysis of three hemodialysis sessions after the second week of treatment.
Time Frame
From the second week of the study until the end (week 6)
Secondary Outcome Measure Information:
Title
Hypotensive episodes
Description
Number of hypotensive episodes during hemodialysis after the second week of treatment
Time Frame
From the second week of the study until the end (week 6)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jorge L Gamboa, M.D. Ph.D.
Phone
6153434176
Email
jorge.gamboa@vumc.org
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jorge L Gamboa, M.D. Ph.D.
Phone
615-343-4176
Email
jorge.gamboa@vanderbilt.edu
First Name & Middle Initial & Last Name & Degree
Jorge L Gamboa, MD Ph.D
First Name & Middle Initial & Last Name & Degree
Talat Alp Ikizler, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

Hemodialysis.-Induced Hypotension Therapy for End Stage Kidney Disease

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