Clinical trial NCT00916643: Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
Official title: Post Marketing Surveillance Study for LDL Apheresis Using H.E.L.P. Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Familial Hypercholesterolemia
Keywords: Hypercholesterolemia
FH
LDL-C
CHD
Lead sponsor: B. Braun Medical Inc.
Sponsor class: INDUSTRY
First posted: 2009-06-09
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objectives of this post-surveillance study are to continue to evaluate the safety and effectiveness of the H.E.L.P. System. The safety and effectiveness will be assessed by evaluating the occurrence of death, cardiovascular events or interventions, angina, and serious unanticipated adverse effects. Laboratory assessments will be made to document low-density lipoprotein cholesterol (LDL-C) reduction and any effects on other blood components. Quality of life assessments will also be made.

The study will also assess the modifications to the H.E.L.P. System, including:

* use of a single heparin adsorber, instead of two smaller adsorbers;
* change in the supplier of the ultrafilter (from Secon to Toray);
* reduction in the number of blood lines from eleven to nine;
* change from a single-layer to a two-layer precipitate filter.

The safety and efficacy of the device specific to these modifications will be evaluated by comparing the safety and efficacy data from the patient registry to the data from the initial clinical study on the device as originally designed.

Detailed description: H.E.L.P. therapy is indicated for use in treating patients with familial hypercholesterolemia (FH) who have undergone six months of optimal diet and drug therapy and whose LDL-C level remains \> 300 mg/dl in the absence of CHD or \> 200 mg/dl with documented CHD. These patients are divided into three subgroups of interest:

* Group A: functional hypercholesterolemic homozygotes with LDL-C \> 500mg/dl;
* Group B: functional hypercholesterolemic heterozygotes with LDL-C \> 300mg/dl;
* Group C: functional hypercholesterolemic heterozygotes with LDL-C \> 200mg/dl and documented CHD.

Optimal diet therapy is defined as having received instruction by a trained dietitian in the use of a diet meeting the National Cholesterol Education Program (NCEP) Step 2 criteria (\< 30% of calories as fat, \< 7% of calories as saturated fat, and \< 200 mg of dietary cholesterol per day). Optimal drug therapy is defined as having been tried on at least two separate classes of effective serum LDL-C lowering agents (\>15% reduction) as currently available for at least six months. These drugs include hydroxy methyl glutaryl (HMG) CoA reductase inhibitors, fibric acid derivatives, niacin, and anion exchange resins. These agents should be used in combination at maximal doses as tolerated by the patient under the supervision of their treating physician to monitor side effects.

Documented coronary heart disease (CHD) includes documentation of coronary heart disease by coronary angiography or a history of myocardial infarction (MI), coronary artery bypass surgery (CABG), percutaneous transluminal coronary angioplasty (PTCA) or alternative revascularization procedure (e.g., atherectomy or stent), or progressive angina documented by exercise or non-exercise stress test.

The primary criteria for evaluating the safety and effectiveness of the device will be:

* Occurrence of Death

  * cardiovascular deaths
  * non-cardiovascular deaths
* Occurrence of Cardiovascular Events

  * MI - stroke
  * unstable angina - transient ischemic attack (TIA)
  * congestive heart failure - pulmonary embolism
  * arrhythmia - peripheral vascular disease
  * hypertension
* Occurrence of Surgical or Non-Surgical Intervention Procedure of the Treatment of Atherosclerotic Cardiovascular Disease (ASCVD) including:

  * coronary artery bypass graft (CABG) surgery
  * peripheral vascular bypass surgery
  * percutaneous transluminal coronary angioplasty (PTCA)
  * percutaneous transluminal coronary artery bypass graft angioplasty
  * percutaneous transluminal peripheral angioplasty (PTA)
  * coronary atherectomy (device)
  * coronary artery bypass graft atherectomy (device)
  * peripheral atherectomy (device)
  * carotid endarterectomy (non-device)
  * peripheral endarterectomy (non-device)
  * coronary artery laser surgery
  * coronary artery bypass graft laser surgery
  * peripheral vascular laser surgery
  * coronary artery stent placement
  * coronary artery bypass graft stent placement
  * peripheral vascular stent placement
  * repair of atherosclerotic aortic and arterial aneurysms
  * limb amputation for ASCVD
* Frequency and severity of CHD Symptoms:

  * chest pain (angina),
  * shortness of breath
  * claudication
* Use of CHD Medications for treatment of:

  * angina
  * heart failure
  * arrhythmias
  * hypertension
  * hyperlipidemia
* Use of Lipid-Lowering Medications and Other Cardiovascular Medications Concomitantly
* Laboratory Assessments (lipid, lipoprotein, chemistry, and clotting factors)
* Quality of life assessments (SF-36)
* Occurrence of Serious and/or Unanticipated Adverse Events Reported During Treatment (e.g., hypotension, nausea, vomiting, syncope)
* Occurrence of other serious illnesses
* Acute Reduction of LDL-C

Eligibility criteria: Inclusion Criteria:

* Adequate venous access
* Laboratory values:

  * Hematocrit 30% or greater
  * platelet count between 100,000 and 1,000,000/ml
* Premenopausal women must be surgically sterilized or be on oral contraceptive therapy and have a negative pregnancy test at the onset of treatment with H.E.L.P.
* Patients have familial hypercholesterolemia and have undergone at least 6 months optimal diet and drug therapy and fit group A, B, or C

Exclusion Criteria:

* Presence of any of the following conditions:

  * untreated hypothyroidism
  * decompensated congestive heart failure
  * major arrhythmia
  * uncontrolled diabetes mellitus
  * any malignancy
  * disorders associated with excessive bleeding (e.g., peptic ulcer and hemophilia)
  * established or suspected intracranial disease which might cause intracranial bleeding if the patient is anticoagulated
  * any other medical disorders which lead the treating physician to believe that H.E.L.P. treatment would not be in the best interest of the patient
  * current treatment with anticoagulants
  * diastolic BP \> 100 mmHg recorded in two occasions at least 24 hours apart.
  * patients under 18 years of age
  * positive test for Hepatitis \[Type A (IgM) or B\] antigen, Hepatitis C antibody, or HIV (or diagnosis of AIDS)

Primary outcomes:
measure: Occurence of Death
timeFrame: Participants were followed for one (1) year following discontinuation of treatment.
measure: Occurrence of Cardiovascular Events and Interventions
timeFrame: Participants were followed for one (1) year following discontinuation of treatment.
measure: Serious Unexpected Adverse Events
timeFrame: Participants were followed for one (1) year following discontinuation of treatment.
measure: Frequency and Severity of CHD Symptoms (Angina)
timeFrame: Participants were followed for one (1) year following discontinuation of treatment.
Secondary outcomes:
Other outcomes:
Locations:
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