Hemodialysis.-Induced Hypotension Therapy for End Stage Kidney Disease

Hemodialysis Complication Clinical Trial

— Hinder  

Official title:

Prevention of Dialysis-Induced Hypotension by Inhibiting Plasma Kallikrein

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05297786
• Other study ID #: 210633
• Status: Recruiting
• Phase: Phase 2
• Start date: July 27, 2022
• Est. completion date: December 2024

Study information

• Verified date: August 2023
• Source: Vanderbilt University Medical Center
• Contact: Jorge L Gamboa, M.D. Ph.D.
• Phone: 6153434176
• Email: jorge.gamboa[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemodialysis Complication
• Hypotension
• Hypotension of Hemodialysis

Intervention

Drug:
• Lanadelumab Injection [Takhzyro]
Lanadelumab 300 mg subcutaneous injection
• Placebo
Placebo injection

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood Pressure during hemodialysis	Average blood pressure during hemodialysis of three hemodialysis sessions after the second week of treatment.	From the second week of the study until the end (week 6)
Secondary	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)