Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy (Secura)

Post Marketing Surveillance Study for LDL Apheresis Using H.E.L.P. Therapy

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.

Study Overview

• Status: Completed
• Conditions: Familial Hypercholesterolemia
• Intervention / Treatment: Device: HELP Secura (apheresis treatment)

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

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: H.E.L.P. Secura; The H.E.L.P. System is a device composed of multiple modules and their associated disposables which can selectively and continuously remove LDL-cholesterol from plasma by precipitating the LDL-cholesterol with high concentrations of heparin in an acidic buffer and returning the plasma to the patient. Procedure steps: Flushing the system with normal saline.; Filtering whole blood through a 0.2 micron plasma filter for continuous plasma removal.; Mixing the plasma with an equal volume of acetate buffer containing heparin.; Precipitation of LDL as a complex with heparin.; Removing the LDL-heparin precipitate by continuous circulation through a filter.; Removing heparin with use of a heparin adsorber.; Bicarbonate dialysis and ultrafiltration to produce an LDL-free plasma without excess heparin.; Re-mixing the LDL-free plasma with blood coming from the plasma filter and returning the reconstituted blood to the patient.

Device: HELP Secura (apheresis treatment); Process is described in Arm (above).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurence of Death	The Categories listed in the table are the Adverse Events (or similar) that resulted in death.	Participants were followed for one (1) year following discontinuation of treatment.
Occurrence of Cardiovascular Events and Interventions	Adverse Events reported for Cardiovascular disease not directly related to therapy.	Participants were followed for one (1) year following discontinuation of treatment.
Serious Unexpected Adverse Events		Participants were followed for one (1) year following discontinuation of treatment.
Frequency and Severity of CHD Symptoms (Angina)	This is equatable to the incidence of Cardiovascular AEs.	Participants were followed for one (1) year following discontinuation of treatment.

Collaborators and Investigators

• Sponsor: B. Braun Medical Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 1999
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: June 8, 2009
• First Submitted That Met QC Criteria: June 8, 2009
• First Posted (Estimated): June 9, 2009

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Hypercholesterolemia; LDL-C; CHD; FH
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II
• Other Study ID Numbers: BBMI_HELP_Secura