Clinical trial NCT05297786: Hemodialysis.-Induced Hypotension Therapy for End Stage Kidney Disease
Official title: Prevention of Dialysis-Induced Hypotension by Inhibiting Plasma Kallikrein
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hemodialysis Complication
Hypotension of Hemodialysis
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2022-03-28
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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


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

Primary outcomes:
measure: Blood Pressure during hemodialysis
timeFrame: From the second week of the study until the end (week 6)
Secondary outcomes:
measure: Hypotensive episodes
timeFrame: From the second week of the study until the end (week 6)
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
References: