Cirrhosis, Thrombocytopenia
Conditions
Keywords
Thrombocytopenia, cirrhosis, Therasphere®, Y90, Radioembolization
Brief summary
Evaluate the safety and efficacy of Yttrium-90 (90Y) radioembolization for the management of thrombocytopenia.
Detailed description
This protocol will provide access to TheraSphere® treatment for patients who have refractory thrombocytopenia secondary to cirrhosis. This protocol will utilize splenic artery-directed TheraSphere® treatment.
Interventions
DEVICETheraSphere® Yttrium-90 Glass Microspheres, BTG International Inc.
The Interventional Radiologists will inject a dose of Yttrium 90 into your spleen through a small catheter placed in your femoral artery.The entire treatment visit is an outpatient procedure. You will only be admitted to the hospital if the physician deems it necessary due to any symptoms you may experience after the treatment is given. This visit may take 6 to 8 hours.
Sponsors
BTG International Inc.
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, 18 years of age or older, of any ethnic or racial group. * Diagnosis of cirrhosis or portal hypertension with a serum platelet count less than or equal to 80 × 109/L. \[Rationale: platelet count \<100 × 109/L triples the rate of liver-related adverse events (3) and worsens postoperative survival in the setting of hepatocellular carcinoma (HCC) (4). Initial platelet count of 80 × 109/L can allow the majority of patients who successfully respond to 90Y-RE (clinical endpoint of 50% platelet count increase) to exceed the 100 × 109/L threshold.\] Cirrhosis is defined by one of three criteria: * Liver Biopsy/histology consistent with cirrhotic architectural liver changes * Portal hypertension (Hepatic venous pressure gradient ≥10 mm Hg) * Evidence of esophageal and/or gastric varices * Patients must have evidence of splenomegaly as determined by screening cross-sectional imaging. * No evidence of myelosuppression (e.g. lymphopenia) as evidenced by normal hematology values at Screening * Adequate baseline organ function(with the exception of cirrhosis) as evidenced by normal BUN/Cr and electrolytes on screening chemistry. * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2 * Patient has a life expectancy of greater than 6 months without intervention. * Patient is willing to participate in the study and has signed the study informed consent. * Women of childbearing potential must have a negative serum pregnancy test within 28 days prior to screening and must not be breastfeeding.
Exclusion criteria
* Patients with serum platelet count less than 10 × 109/L. * History of bleeding disorder attributed to another cause other than cirrhosis (e.g. Von Willebrand disease) * Declines or unable to provide informed consent * History of prior partial splenic embolization (PSE) or splenectomy * Use of any medication known to increase platelet count 1 month prior to Baseline. * History of allergy or sensitivity to TheraSphere® or its components. * History of severe peripheral allergy or intolerance to contrast agents, narcotics, sedatives or atropine that cannot be managed medically * Contraindications to angiography and selective visceral catheterization such as bleeding, diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g. closure device) * Previous randomization in a trial using 90Y RE * Patient must not have participated or enrolled in a clinical trial with an investigational device / therapy within 30 days prior to randomization * Any serious medical condition likely to impede successful completion of the study, such as certain mental disorders, cardiac arrhythmias, and uncontrolled congestive heart failure or respiratory disease. * Patients actively on chemotherapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Objective of This Pilot Study is to Evaluate the Safety of 90Y TARE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Evaluation of Overall AE Reporting in All Categories. | 6 months | The number and the severity of ALL adverse events will be recorded to evaluate safety. Events will be reported by subjects at follow up visits. Scale: Common Terminology Criteria for Adverse Events (CTCAE) CT CAE v 4.0.3 Grades range from 1-5 with 5 being the worst (Death), descriptions of each grade for specific AE's are available here: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE\_4.03/CTCAE\_4.03\_2010-06-14\_QuickReference\_8.5x11.pdf Total AE's of different types are collected and for each grade are reported as a group |
| Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Reporting of Splenic Abscess. | 6 months | The number and the severity of adverse events related to splenic abscess will be recorded to evaluate safety. Events will be reported by subjects at follow up visits. Scale: Common Terminology Criteria for Adverse Events (CTCAE) CT CAE v 4.0.3 Grades range from 1-5 with 5 being the worst (Death), Grade 1 (Mild):Small abscess with minimal symptoms, often not requiring intervention. Grade 2 (Moderate):Larger abscess causing moderate symptoms, may require antibiotics or drainage procedures. Grade 3 (Severe):Large abscess with significant symptoms, potentially causing systemic effects, requiring hospitalization and aggressive management. Grade 4 (Life-threatening):Abscess with immediate life-threatening complications, requiring urgent intervention. Grade 5 Death |
| Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. AE's Related to Infection. | 6 months | The number and the severity of adverse events related to infection will be recorded to evaluate safety. Events will be reported by subjects at follow up visits. Common Terminology Criteria for Adverse Events (CTCAE) CT CAE v 4.0.3, Grades range from 1-5 with 5 being the worst (Death) Grade 1 (Mild): Asymptomatic or mild symptoms, only requiring clinical observation, no intervention needed. Grade 2 (Moderate): Symptoms limiting some daily activities, minimal intervention may be required. Grade 3 (Severe): Symptoms significantly impacting self-care, requiring hospitalization or prolonged stay. Grade 4 (Life-threatening): Urgent intervention needed due to life-threatening complications. Grade 5 (Death): Death directly related to the infection. |
| Asses the Need for Technetium Albumin Aggregated (TC-MAA 99m) Injection to Determine Shunting Prior to Y90 Administration | 6 months | MAA injection will be done and nuclear medicine PET scan to evaluate shunting and evaluated for the first 4 patients. If shunt is \<5% subsequently enrolled patients will not undergo MAA, if shunt is \>5% all subsequent patients will undergo MAA. This will be evaluated post MAA injection before Y90 treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Achieve 20% Decrease in Functional Splenic Volume Six Months After Treatment | 6 months | Assessed via cross sectional CT or MR of the abdomen at screening and at 4 weeks, 3 months, and 6 months post treatment. Comparison made with screening CT or MR and 6 month follow up imaging. |
| Evaluate Length of Hospital Stay After Procedure | 6 months | Determine the average length of stay in the hospital in days after treatment. |
| Achieve a 50% Increase in Platelet Count Six Months After Therapy. | 6 months | Complete Blood Count with platelets will be drawn at baseline, treatment, 2, 4, 6, 8 weeks and 3, 4, 5, 6 months post treatment. Comparison made with screening platelet count and 6 month follow up visit platelet count. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subjects With Thrombocytopenia Secondary to Cirrhosis Evaluate the safety and efficacy of 90Y radioembolization for the management of thrombocytopenia.
TheraSphere® Yttrium-90 Glass Microspheres, BTG International Inc.: The Interventional Radiologists will inject a dose of Yttrium 90 into your spleen through a small catheter placed in your femoral artery. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Subjects With Thrombocytopenia Secondary to Cirrhosis |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 61 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 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 | 1 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 | 6 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Asses the Need for Technetium Albumin Aggregated (TC-MAA 99m) Injection to Determine Shunting Prior to Y90 Administration
MAA injection will be done and nuclear medicine PET scan to evaluate shunting and evaluated for the first 4 patients. If shunt is \<5% subsequently enrolled patients will not undergo MAA, if shunt is \>5% all subsequent patients will undergo MAA. This will be evaluated post MAA injection before Y90 treatment.
Time frame: 6 months
Population: All four patients that received Tc-MAA to determine shunting prior to Y90 RE had a lung shunt fraction \<5%. Given this finding no subsequent patients needed MAA or lung shunt study performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Asses the Need for Technetium Albumin Aggregated (TC-MAA 99m) Injection to Determine Shunting Prior to Y90 Administration | 0 participants |
Primary
Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. AE's Related to Infection.
The number and the severity of adverse events related to infection will be recorded to evaluate safety. Events will be reported by subjects at follow up visits. Common Terminology Criteria for Adverse Events (CTCAE) CT CAE v 4.0.3, Grades range from 1-5 with 5 being the worst (Death) Grade 1 (Mild): Asymptomatic or mild symptoms, only requiring clinical observation, no intervention needed. Grade 2 (Moderate): Symptoms limiting some daily activities, minimal intervention may be required. Grade 3 (Severe): Symptoms significantly impacting self-care, requiring hospitalization or prolonged stay. Grade 4 (Life-threatening): Urgent intervention needed due to life-threatening complications. Grade 5 (Death): Death directly related to the infection.
Time frame: 6 months
Population: 3 subjects reported infections these were unrelated to treatment on study. Pneumonia grade 3, lung infection grade 3, vaginal infection grade 2. All resolved before the study was completed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. AE's Related to Infection. | Grade 1 | 0 events |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. AE's Related to Infection. | Grade 2 | 1 events |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. AE's Related to Infection. | Grade 3 | 2 events |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. AE's Related to Infection. | Grade 4 | 0 events |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. AE's Related to Infection. | Grade 5 | 0 events |
Primary
Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Reporting of Splenic Abscess.
The number and the severity of adverse events related to splenic abscess will be recorded to evaluate safety. Events will be reported by subjects at follow up visits. Scale: Common Terminology Criteria for Adverse Events (CTCAE) CT CAE v 4.0.3 Grades range from 1-5 with 5 being the worst (Death), Grade 1 (Mild):Small abscess with minimal symptoms, often not requiring intervention. Grade 2 (Moderate):Larger abscess causing moderate symptoms, may require antibiotics or drainage procedures. Grade 3 (Severe):Large abscess with significant symptoms, potentially causing systemic effects, requiring hospitalization and aggressive management. Grade 4 (Life-threatening):Abscess with immediate life-threatening complications, requiring urgent intervention. Grade 5 Death
Time frame: 6 months
Population: All subjects treated on study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Reporting of Splenic Abscess. | Grade 1 | 0 events |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Reporting of Splenic Abscess. | Grade 2 | 0 events |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Reporting of Splenic Abscess. | Grade 3 | 0 events |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Reporting of Splenic Abscess. | Grade 4 | 0 events |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Reporting of Splenic Abscess. | Grade 5 | 0 events |
Primary
The Primary Objective of This Pilot Study is to Evaluate the Safety of 90Y TARE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Evaluation of Overall AE Reporting in All Categories.
The number and the severity of ALL adverse events will be recorded to evaluate safety. Events will be reported by subjects at follow up visits. Scale: Common Terminology Criteria for Adverse Events (CTCAE) CT CAE v 4.0.3 Grades range from 1-5 with 5 being the worst (Death), descriptions of each grade for specific AE's are available here: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE\_4.03/CTCAE\_4.03\_2010-06-14\_QuickReference\_8.5x11.pdf Total AE's of different types are collected and for each grade are reported as a group
Time frame: 6 months
Population: All subjects enrolled received treatment per protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects With Thrombocytopenia Secondary to Cirrhosis | The Primary Objective of This Pilot Study is to Evaluate the Safety of 90Y TARE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Evaluation of Overall AE Reporting in All Categories. | Grade 3 AE | 28 events |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | The Primary Objective of This Pilot Study is to Evaluate the Safety of 90Y TARE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Evaluation of Overall AE Reporting in All Categories. | Grade 1 AE | 49 events |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | The Primary Objective of This Pilot Study is to Evaluate the Safety of 90Y TARE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Evaluation of Overall AE Reporting in All Categories. | Grade 2 AE | 34 events |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | The Primary Objective of This Pilot Study is to Evaluate the Safety of 90Y TARE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Evaluation of Overall AE Reporting in All Categories. | Grade 4 AE | 15 events |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | The Primary Objective of This Pilot Study is to Evaluate the Safety of 90Y TARE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Evaluation of Overall AE Reporting in All Categories. | Grade 5 AE | 0 events |
Secondary
Achieve 20% Decrease in Functional Splenic Volume Six Months After Treatment
Assessed via cross sectional CT or MR of the abdomen at screening and at 4 weeks, 3 months, and 6 months post treatment. Comparison made with screening CT or MR and 6 month follow up imaging.
Time frame: 6 months
Population: All subjects had a CT or MR at screening, 1 month, 3 months, and 6moths timepoints. Splenic volumes were reported at all time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Achieve 20% Decrease in Functional Splenic Volume Six Months After Treatment | Achieved 20% decrease in volume | 1 participants |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Achieve 20% Decrease in Functional Splenic Volume Six Months After Treatment | Did not achieve 20% decrease in volume | 6 participants |
Secondary
Achieve a 50% Increase in Platelet Count Six Months After Therapy.
Complete Blood Count with platelets will be drawn at baseline, treatment, 2, 4, 6, 8 weeks and 3, 4, 5, 6 months post treatment. Comparison made with screening platelet count and 6 month follow up visit platelet count.
Time frame: 6 months
Population: The 7 participating subjects had platelets drawn 6 months post procedure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Achieve a 50% Increase in Platelet Count Six Months After Therapy. | Achieved 50% increase in 6 months | 0 participants |
| Subjects With Thrombocytopenia Secondary to Cirrhosis | Achieve a 50% Increase in Platelet Count Six Months After Therapy. | Did not achieve 50% increase in 6 months | 7 participants |
Secondary
Evaluate Length of Hospital Stay After Procedure
Determine the average length of stay in the hospital in days after treatment.
Time frame: 6 months
Population: no subjects were admitted after their procedure so there are 0 days hospitalized to report or analyze.