Post Approval Study of Lixelle for the Treament of Dialysis-Related Amyloidosis

In a post-market study on Lixelle® conducted between 1994 and 1997 in Japan, all adverse events in 183 patients (13, 476 treatments) at 58 centers were collected. The most frequent adverse events were temporary hypotension and anemia, which are common in dialysis or any extracorporeal therapy. Since the maximum blood flow rate for Lixelle® is less than the average blood flow rate for the conventional HD in the USA, Lixelle®- treatment requires a longer treatment time to achieve the same Kt/V urea as the conventional HD in the United States. However, the longer dialysis time and the lower blood flow rate are not likely to increase the rate of adverse events. Adverse events (including Serious Adverse Events) will be collected at each treatment whenever they occur and will be analyzed using descriptive statistics.

This is a prospective double-armed study of 2 years of Lixelle®-treatment. The study consists of the study arm of 2 years of Lixelle®-treatment in 30 DRA patients and the natural history arm of 2 years of conventional HD in 10 DRA patients as the descriptive reference.

The primary objective of this study is to assess the safety of Lixelle® in patients in the USA. The secondary objectives of this study are to assess the probable benefit of Lixelle® to increase the β2M reduction rate in a single dialysis session.

Exploratory endpoints are to assess:

• the changes of DRA symptoms and ADL of the patients treated with Lixelle® using DRAQ (Dialysis-Related Amyloidosis Questionnaire)
• the changes of QOL of the patients treated with Lixelle® using KDQOL-SF (Kidney Disease Quality of Life Short Form)
• the pre-treatment β2M levels at baseline, one and two years; and
• bone cysts at baseline and two years

Inclusion criteria

• Patients receiving thrice-weekly HD and diagnosed as DRA by one or more of the following 1 to 4 will be included.

• Biopsy of any tissue, showing Congo-red positive amyloid fibrils and immunohistochemical stains consistent with β2M
• Shoulder ultrasonography showing rotator cuffs greater than 8 mm in thickness, and /or echogenic pads between muscle groups of the rotator cuff
• Two or more diagnoses of the following (1) to (5) (1) Polyarthralgia (2) Carpal tunnel syndrome (3) Trigger finger (4) Dialysis-associated spondylosis ((i) or (ii)) (i) Destructive spondyloarthropathy (DSA) (ii) Spinal stenosis (5) Bone cysts (Bone cysts considered to be caused by other diseases such as osteoarthritis, aneurysmal bone cysts and unicameral bone cysts should be excluded.)
• Biopsy of any tissue, showing Congo-red positive amyloid fibrils, and one diagnosis or surgical history of criterion 3- (1) to (5)

Exclusion criteria

• Patient who meets any of the following 1 to 7 will be excluded from the study.

• Patient diagnosed with rheumatoid arthritis
• Patient diagnosed with osteoporosis
• Patient diagnosed with osteoarthritis
• Patient planning to receive renal transplantation during the study
• Patient for whom adequate anticoagulation cannot be achieved
• Patient for whom extracorporeal circulation therapy is contraindicated, such as those with severe cardiac insufficiency, acute myocardial infarction, severe cardiac arrhythmia, acute seizure disorder, or severe uncontrolled hypertension or hypotension
• Patient planning to become pregnant, pregnant, or breast-feeding
• Patient unable to understand or answer the questionnaires even with a proper assistance