Hypercholesterolemia
Conditions
Keywords
Heparin, Extracorporeal, Low Density Lipo-Protein (LDL) Cholesterol, Apheresis, Device
Brief summary
The primary objective of the study is to demonstrate that the performance of the modified Plasmat® Futura H.E.L.P. Apheresis System is non-inferior to the current FDA approved Plasmat® Secura H.E.L.P Apheresis System for use under the approved indication of the acute reduction of LDL-cholesterol from the plasma in populations for whom diet has been ineffective and maximum drug therapy has either been ineffective or not tolerated.
Detailed description
The primary study endpoint is the change in percent measurements of the pre-to-post apheresis LDL measurements between the approved H.E.L.P. system and the modified H.E.L.P. system. The secondary study endpoints are clinical lab profiles and device parameters analyzed at specific time points throughout the study.
Interventions
DEVICESecura then Futura
Randomized to 6 bi-monthly H.E.L.P. therapy treatments with the Plasmat® Secura apheresis system and then cross over to receive 6 bi-monthly treatments with the Plasmat® Futura apheresis system.
DEVICEFutura then Secura
Randomized to 6 bi-monthly H.E L.P. therapy treatments with the Plasmat® Futura apheresis system and then cross over to receive 6 bi-monthly treatments with the Plasmat® Secura apheresis system.
Sponsors
B. Braun Medical Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Subject is between 25 and 70 years of age (inclusive) at the time of randomization. * Subject is an appropriate candidate for H.E.L.P. apheresis treatment for hypercholesterolemia according to current Plasmat® Secura approval criteria. * Subject has received a minimum of two consecutive bi-monthly\* H.E.L.P. apheresis treatments using the Plasmat® Secura apheresis system \>30 days prior to the screening visit. * Subject is willing to maintain cholesterol lowering dietary and drug therapies as prescribed through the course of the study. * Subject is willing and able to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) Waiver. * Sterile, post-menopausal, or using acceptable birth control for the duration of the study. Acceptable birth control is defined as having a vasectomized, postmenopausal, or sterile partner; the ongoing use of approved hormonal contraceptives, barrier method, or an intrauterine device; or abstinence. * Every 14 days (±2 days)
Exclusion criteria
* A History of a known sensitivity to heparin or ethylene oxide. * A history of hemorrhagic diathesis, bleeding/clotting disorder, thrombocytopenia (defined as platelet count \< 150 x109/L), or for whom the use of heparin would cause excessive or uncontrolled anticoagulation or for whom adequate anticoagulation cannot be safely achieved (ie., hemophilia, recent surgery, acute internal bleeding, gastrointestinal ulcers). * Females who are pregnant or lactating. * Subjects\< 106 lbs. or \<48.2 kg in body weight; or whose weight is \>1.5 times their ideal weight. * Certain cardiac impairments such as congestive heart failure, major arrhythmia, or diastolic blood pressure greater than 100 mm/Hg on two separate occasions at least 24 hours apart. * Renal insufficiency defined as creatinine greater \>2.0 mg/dlL or is dependent upon renal dialysis. * Untreated hypothyroidism; uncontrolled diabetes mellitus; or fasting triglycerides \>500 mg/dL. * Serious systemic disease (e.g., advanced neoplasms, and acute hepatitis) including Immune system suppression or compromise, that could preclude survival to study completion. * History of stroke within 6 months of the screening visit. * Received thrombolytic treatment \< 7 days of screening.visit. * Taken or requires a prohibited treatment \< 30 days prior to the Screening Visit, or requires a prohibited treatment at anytime during the course of the study. * Neutropenia (neutrophil count \< 0.5 x109/L). * History of liver disease or serum ALT and/or AST \> 2X upper limit of normal range. * History of dementia. * History of anemia (value outside the lower normal range). * acetyl salicylic acid (ASA) \> 325 mg/day. * Subject currently enrolled in another investigational study (does not apply to PMS for Secura device). * Subject with any other medical condition that in the opinion of the investigator might put the subject at risk or interfere with his/her participation. * Subject is unwilling or unable to comply with the protocol or to cooperate fully with the investigator or site personnel.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Pre- and Post-treatment Reductions of Low-density Lipoprotein Cholesterol (LDL-C) Levels Between the Approved H.E.L.P. System and the Modified H.E.L.P. System. | Blood samples for LDL-cholesterol determination will be obtained before and after each treatment from week 0 to week 24.. | — |
| Percent Change of the Pre and Post Treatment Value | Assessment based on LDL-C values obtained pre-and post-treatment, analyzed from week 0 to week 24. | The primary study endpoint is the change in percent measurements of the pre-to-post apheresis LDL measurements. Blood samples for LDL-cholesterol determination will be obtained before and after each treatment. The pooled difference between the pre- and post-treatment LDL level for each apheresis machine will be reported as the primary endpoint for the system performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Lab Profiles (Pre- and Post-Treatment) | Analyzed at specific time points throughout the study from week 0 to week 24. | Changes in pre- and post-treatment levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), total triglycerides, lipoprotein (a), fibrinogen, and C-reactive protein. |
| Device Parameters | Analyzed at specific time points throughout the study from week 0 to week 24. | Comparison of plasma flow rate recorded with both systems before treatment, after 500 mL of plasma treated, and at the end of each treatment session. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Secura Randomized first to the approved Plasmat® Secura apheresis system then Plasmat® Futura apheresis system. | 9 |
| Futura Randomized first to the approved Plasmat® Futura apheresis system then Plasmat® Secura apheresis system. | 9 |
| Total | 18 |
Baseline characteristics
| Characteristic | Secura | Total | Futura |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 5 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 13 Participants | 6 Participants |
| Age, Continuous | 57.0 years STANDARD_DEVIATION 7.76 | 58.3 years STANDARD_DEVIATION 8.35 | 59.7 years STANDARD_DEVIATION 9.15 |
| Region of Enrollment United States | 9 participants | 18 participants | 9 participants |
| Sex: Female, Male Female | 6 Participants | 12 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 18 | 17 / 18 |
| serious Total, serious adverse events | 4 / 18 | 1 / 18 |
Outcome results
Primary
Percent Change in Pre- and Post-treatment Reductions of Low-density Lipoprotein Cholesterol (LDL-C) Levels Between the Approved H.E.L.P. System and the Modified H.E.L.P. System.
Time frame: Blood samples for LDL-cholesterol determination will be obtained before and after each treatment from week 0 to week 24..
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Secura | Percent Change in Pre- and Post-treatment Reductions of Low-density Lipoprotein Cholesterol (LDL-C) Levels Between the Approved H.E.L.P. System and the Modified H.E.L.P. System. | 55.28 percent change |
| Futura | Percent Change in Pre- and Post-treatment Reductions of Low-density Lipoprotein Cholesterol (LDL-C) Levels Between the Approved H.E.L.P. System and the Modified H.E.L.P. System. | 52.89 percent change |
Primary
Percent Change of the Pre and Post Treatment Value
The primary study endpoint is the change in percent measurements of the pre-to-post apheresis LDL measurements. Blood samples for LDL-cholesterol determination will be obtained before and after each treatment. The pooled difference between the pre- and post-treatment LDL level for each apheresis machine will be reported as the primary endpoint for the system performance.
Time frame: Assessment based on LDL-C values obtained pre-and post-treatment, analyzed from week 0 to week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Secura | Percent Change of the Pre and Post Treatment Value | 55.28 percent change | Standard Deviation 9.783 |
| Futura | Percent Change of the Pre and Post Treatment Value | 52.89 percent change | Standard Deviation 8.228 |
p-value: 0.005ANOVA
Secondary
Clinical Lab Profiles (Pre- and Post-Treatment)
Changes in pre- and post-treatment levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), total triglycerides, lipoprotein (a), fibrinogen, and C-reactive protein.
Time frame: Analyzed at specific time points throughout the study from week 0 to week 24.
Population: Data for all 18 subjects; regardless of treatment sequence
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Secura | Clinical Lab Profiles (Pre- and Post-Treatment) | HDL-C | 11.82 percent change |
| Secura | Clinical Lab Profiles (Pre- and Post-Treatment) | Lipoprotein (a) | 59.25 percent change |
| Secura | Clinical Lab Profiles (Pre- and Post-Treatment) | VLDL-C | 62.14 percent change |
| Secura | Clinical Lab Profiles (Pre- and Post-Treatment) | Fibrinogen | 54.81 percent change |
| Secura | Clinical Lab Profiles (Pre- and Post-Treatment) | Total Cholesterol | 50.23 percent change |
| Secura | Clinical Lab Profiles (Pre- and Post-Treatment) | C-Reactive Protein | 58.59 percent change |
| Secura | Clinical Lab Profiles (Pre- and Post-Treatment) | Total Triglycerides | 63.17 percent change |
| Futura | Clinical Lab Profiles (Pre- and Post-Treatment) | C-Reactive Protein | 48.88 percent change |
| Futura | Clinical Lab Profiles (Pre- and Post-Treatment) | Total Triglycerides | 71.46 percent change |
| Futura | Clinical Lab Profiles (Pre- and Post-Treatment) | Total Cholesterol | 48.12 percent change |
| Futura | Clinical Lab Profiles (Pre- and Post-Treatment) | HDL-C | 7.41 percent change |
| Futura | Clinical Lab Profiles (Pre- and Post-Treatment) | VLDL-C | 62.65 percent change |
| Futura | Clinical Lab Profiles (Pre- and Post-Treatment) | Lipoprotein (a) | 49.68 percent change |
| Futura | Clinical Lab Profiles (Pre- and Post-Treatment) | Fibrinogen | 52.00 percent change |
Secondary
Device Parameters
Comparison of plasma flow rate recorded with both systems before treatment, after 500 mL of plasma treated, and at the end of each treatment session.
Time frame: Analyzed at specific time points throughout the study from week 0 to week 24.
Population: Data for all 18 subjects; regardless of treatment sequence
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Secura | Device Parameters | Start of Session; Session 5 | 26.29 flow rate (mL/min) | Standard Deviation 6.049 |
| Secura | Device Parameters | After 500mL; Session 4 | 32.11 flow rate (mL/min) | Standard Deviation 3.216 |
| Secura | Device Parameters | Start of Session; Session 3 | 28.00 flow rate (mL/min) | Standard Deviation 13.711 |
| Secura | Device Parameters | After 500mL; Session 5 | 34.67 flow rate (mL/min) | Standard Deviation 5.018 |
| Secura | Device Parameters | Start of Session; Session 6 | 27.61 flow rate (mL/min) | Standard Deviation 7.92 |
| Secura | Device Parameters | After 500mL; Session 6 | 32.72 flow rate (mL/min) | Standard Deviation 8.456 |
| Secura | Device Parameters | Start of Session; Session 2 | 23.41 flow rate (mL/min) | Standard Deviation 10.978 |
| Secura | Device Parameters | After 500mL; Session 1 | 33.67 flow rate (mL/min) | Standard Deviation 6.38 |
| Secura | Device Parameters | End of session; Session 2 | 27.87 flow rate (mL/min) | Standard Deviation 16.587 |
| Secura | Device Parameters | Start of Session; Session 4 | 26.35 flow rate (mL/min) | Standard Deviation 8.838 |
| Secura | Device Parameters | End of session; Session 3 | 19.17 flow rate (mL/min) | Standard Deviation 15.946 |
| Secura | Device Parameters | After 500mL; Session 2 | 32.59 flow rate (mL/min) | Standard Deviation 5.938 |
| Secura | Device Parameters | End of session; Session 4 | 28.00 flow rate (mL/min) | Standard Deviation 15.326 |
| Secura | Device Parameters | Start of Session; Session 1 | 27.11 flow rate (mL/min) | Standard Deviation 9.38 |
| Secura | Device Parameters | End of session; Session 5 | 30.28 flow rate (mL/min) | Standard Deviation 12.75 |
| Secura | Device Parameters | After 500mL; Session 3 | 31.61 flow rate (mL/min) | Standard Deviation 4.354 |
| Secura | Device Parameters | End of session; Session 6 | 28.59 flow rate (mL/min) | Standard Deviation 15.133 |
| Secura | Device Parameters | End of session; Session 1 | 26.24 flow rate (mL/min) | Standard Deviation 16.51 |
| Futura | Device Parameters | End of session; Session 6 | 29.06 flow rate (mL/min) | Standard Deviation 5.043 |
| Futura | Device Parameters | Start of Session; Session 1 | 12.39 flow rate (mL/min) | Standard Deviation 5.203 |
| Futura | Device Parameters | Start of Session; Session 2 | 8.89 flow rate (mL/min) | Standard Deviation 4.31 |
| Futura | Device Parameters | Start of Session; Session 3 | 9.67 flow rate (mL/min) | Standard Deviation 3.664 |
| Futura | Device Parameters | Start of Session; Session 4 | 9.17 flow rate (mL/min) | Standard Deviation 5.079 |
| Futura | Device Parameters | Start of Session; Session 5 | 10.12 flow rate (mL/min) | Standard Deviation 3.998 |
| Futura | Device Parameters | Start of Session; Session 6 | 8.39 flow rate (mL/min) | Standard Deviation 3.898 |
| Futura | Device Parameters | After 500mL; Session 1 | 23.44 flow rate (mL/min) | Standard Deviation 2.895 |
| Futura | Device Parameters | After 500mL; Session 2 | 22.50 flow rate (mL/min) | Standard Deviation 3.552 |
| Futura | Device Parameters | After 500mL; Session 3 | 22.71 flow rate (mL/min) | Standard Deviation 3.601 |
| Futura | Device Parameters | After 500mL; Session 4 | 23.11 flow rate (mL/min) | Standard Deviation 4.861 |
| Futura | Device Parameters | After 500mL; Session 5 | 21.41 flow rate (mL/min) | Standard Deviation 3.501 |
| Futura | Device Parameters | After 500mL; Session 6 | 23.72 flow rate (mL/min) | Standard Deviation 2.967 |
| Futura | Device Parameters | End of session; Session 1 | 32.24 flow rate (mL/min) | Standard Deviation 17.922 |
| Futura | Device Parameters | End of session; Session 2 | 28.44 flow rate (mL/min) | Standard Deviation 8.748 |
| Futura | Device Parameters | End of session; Session 3 | 26.44 flow rate (mL/min) | Standard Deviation 9.281 |
| Futura | Device Parameters | End of session; Session 4 | 23.29 flow rate (mL/min) | Standard Deviation 7.928 |
| Futura | Device Parameters | End of session; Session 5 | 21.50 flow rate (mL/min) | Standard Deviation 10.671 |