Hemodialysis Complication, Hypotension of Hemodialysis
Conditions
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
Interventions
DRUGLanadelumab Injection [Takhzyro]
Lanadelumab 300 mg subcutaneous injection
DRUGPlacebo
Placebo injection
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure During Hemodialysis | Pre-hemodialysis and post-hemodialysis, up to 4.5 hours, at baseline and at the end of the study (week 6) | Systolic blood pressure pre and post hemodialysis at baseline and at the end of the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Episodes | From the first week of the study until the end (week 6) | Number of hypotensive episodes during hemodialysis after the initiation of the treatment |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 60.9 years STANDARD_DEVIATION 15.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 4 / 14 | 8 / 14 |
| serious Total, serious adverse events | 1 / 14 | 3 / 14 |
Outcome results
None listed