Antiphospholipid Antibody Syndrome, End Stage Renal Disease
Conditions
Keywords
CAPS, Kidney transplant, Renal transplant, Catastrophic Antiphospholipid Antibody Syndrome
Brief summary
Catastrophic Antiphospholipid Antibody Syndrome (CAPS) is a rare condition in which life-threatening blood clots form in multiple organs simultaneously and can lead to multi-organ system failure and death. The causes of CAPS are not entirely understood, but CAPS episodes are often triggered by stressful events such as infections, surgery, or trauma. For patients who survive an episode of CAPS, permanent kidney failure is not uncommon because the kidneys are the organ system most frequently affected in CAPS. Kidney transplantation is the treatment of choice for end-stage kidney disease, but patients with a history of CAPS are exceptionally high-risk kidney transplant recipients because the chance that surgery itself could trigger a life-threatening or transplant-threatening episode of CAPS is significant. As a result, patients with CAPS are not generally considered candidates for transplantation. Despite this, these patients have a severely decreased life-expectancy on dialysis and their long-term survival and quality of life would be greatly increased by a successful kidney transplant. In this trial, a drug called eculizumab will be tested for its ability to prevent CAPS after kidney transplantation in patients with a prior history of CAPS. Eculizumab is an inhibitor of the complement system, which is believed to be important in generating the inflammatory environment that leads to diffuse clotting of blood vessels in CAPS. The investigators hypothesize that by blocking the complement cascade using eculizumab, in conjunction with blocking the coagulation system, that kidney transplantation can be safely and successfully performed in patients with a history of CAPS.
Interventions
DRUGEculizumab
Eculizumab will be administered by intravenous infusion. Eculizumab will be administered at a dose of 1200mg by intravenous (IV) infusion on the day of or on the day prior to kidney transplantation, and at a dose of 900mg IV on post-operative day 1. Subsequently, the post-operative dosing regimen would be comprised of an induction phase of weekly doses of 900mg IV per dose followed by a maintenance phase of every other week dosing of 1200mg IV per dose. The weekly induction dosing regimen would begin on postoperative day 8, and would continue for three doses (specifically, doses of 900mg IV would be given on postoperative days 8, 15, and 22). The maintenance phase of dosing would begin with a dose of 1200mg on postoperative day 29, and would continue for a total of 5 doses (specifically, doses of 1200mg IV would be given on postoperative days 29, 43, 47, 72, and 85). In most cases, eculizumab would be discontinued after the 5th maintenance dose.
Sponsors
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * History of Catastrophic Antiphospholipid Antibody Syndrome (CAPS) * End-stage renal disease
Exclusion criteria
* Any contraindications to transplantation other than CAPS * Pregnant women * Women who intend to become pregnant over the study period * Ongoing or untreated meningococcal infections * History of serious adverse reaction to eculizumab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Patients With Prevention of Catastrophic Antiphospholipid Antibody Syndrome (CAPS) After Kidney Transplant | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Number of Patients With Kidney Transplant Graft Survival | 6 months |
| Number of Patients Who Survive | 6 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eculizumab Patients will receive eculizumab in conjunction with systemic anticoagulation before and after kidney transplant operation | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Eculizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Number of Patients With Prevention of Catastrophic Antiphospholipid Antibody Syndrome (CAPS) After Kidney Transplant
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eculizumab | Number of Patients With Prevention of Catastrophic Antiphospholipid Antibody Syndrome (CAPS) After Kidney Transplant | 1 Participants |
Secondary
Number of Patients Who Survive
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eculizumab | Number of Patients Who Survive | 1 Participants |
Secondary
Number of Patients With Kidney Transplant Graft Survival
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eculizumab | Number of Patients With Kidney Transplant Graft Survival | 1 Participants |