Background
Methods
Study design and subjects
Outcome measurement
Sample size determination
Statistical analyses
Results
Patient demographics and baseline characteristics
Total (N = 209) | |
---|---|
Age, years | 47.93 ± 13.10 |
Age group, n (%) | |
< 65 years | 183 (87.56) |
≥ 65 years | 26 (12.44) |
Sex, male, n (%) | 128 (61.24) |
Height, cm | 164.85 ± 8.80 |
Body Weight, kg | 61.73 ± 10.75 |
Allergy history, n (%) | 5 (2.39) |
Secondary transplantation, n (%) | 10 (4.78%) |
Primary cause of kidney failure, n (%) | |
Hypertension | 56 (26.79) |
Diabetes mellitus | 33 (15.79) |
Glomerulonephritis | 55 (26.32) |
Polycystic kidney disease | 11 (5.26) |
Others | 54 (25.84) |
Panel reactive antibody of recipients (%) | |
Class I | 6.35 ± 21.50 |
Class II | 5.89 ± 17.39 |
Type of donation, n (%) | |
Living donor | 132 (63.46) |
Deceased donor | 76 (36.54) |
Age of donors, years | 41.49 ± 13.16 |
Past general medical history, n (%)a | 141 (67.46%) |
Liver disease, n (%) | 13 (6.22%) |
Concomitant immunosuppressive medication, n (%)b | |
Monotherapy | 44 (21.05) |
Dual therapy | 140 (66.99) |
Triple therapy | 25 (11.96) |
Trough level of cyclosporine, ng/mL | |
Immunoassay | 72.84 ± 47.01 |
HPLC method | 100.18 ± 64.80 |
Trough level of tacrolimus, ng/mL | |
Immunoassay | 4.34 ± 1.77 |
HPLC method | 4.51 ± 3.25 |
Trough level of mycophenolic acid, ng/mL | |
HPLC method | 1.53 ± 0.86 |
Time between transplantation and the first administration of Rapamune, days, median (range) | median 909 (range: 9 to 10,816) |
< 6 months, n (%) | 28 (13.40) |
6 months to < 1 year, n (%) | 20 (9.57) |
1 year to < 5 years, n (%) | 94 (44.98) |
≥ 5 years, n (%) | 65 (31.10) |
Total administration period of Rapamune, days | median 182 (range: 4 to 971) |
< 6 months, n (%) | 96 (45.93) |
6 month to < 1 year, n (%) | 99 (47.37) |
≥ 1 year, n (%) | 14 (6.70) |
Daily dose of Rapamune, mg | 1.79 ± 0.68 |
< 2 mg, n (%) | 112 (53.59) |
2 mg, n (%) | 46 (22.01) |
> 2 mg, n (%) | 51 (24.40) |
Trough level of Rapamune, ng/mL | |
Immunoassay | 5.45 ± 2.59 |
HPLC method | 7.87 ± 4.24 |
Immunosuppressive medications
Safety
Systemic organ class and preferred terma | Total (N = 209) | |
---|---|---|
Number of Subjects (%) | Number of Adverse Events | |
Resistance mechanism disorders | ||
Infection susceptibility increased | 1 (0.48) | 1 |
Polyomavirus infection | 1 (0.48) | 1 |
Gastro-intestinal system disorders | ||
Diarrhoea | 5 (2.39) | 5 |
Stomatitis | 3 (1.44) | 3 |
Stomatitis ulcerative | 1 (0.48) | 1 |
Abdominal pain | 2 (0.96) | 2 |
Nausea | 1 (0.48) | 1 |
Urinary system disorders | ||
Azotaemia | 6 (2.87) | 6 |
Albuminuria | 1 (0.48) | 1 |
Oliguria | 1 (0.48) | 1 |
Skin and appendages disorders | ||
Acne | 1 (0.48) | 1 |
Rash | 1 (0.48) | 1 |
Rash erythematous | 2 (0.96) | 2 |
Dermatitis | 1 (0.48) | 1 |
Metabolic and nutritional disorders | ||
Diabetes mellitus | 1 (0.48) | 1 |
Diabetes mellitus aggravated | 1 (0.48) | 1 |
Plasma osmolality increased | 1 (0.48) | 1 |
Body as a whole– general disorders | ||
Edema peripheral | 1 (0.48) | 1 |
Face edema | 2 (0.96) | 2 |
Anaphylactic reaction | 1 (0.48) | 1 |
Liver and biliary system disorders | ||
Hepatic function abnormal | 1 (0.48) | 1 |
Cholangitis | 1 (0.48) | 1 |
Musculo-skeletal system disorders | ||
Avascular necrosis bone | 1 (0.48) | 1 |
Secondary terms – events | ||
Transplant rejection | 2 (0.96) | 2 |
Respiratory system disorders | ||
Coughing (≥ 4 weeks) | 1 (0.48) | 1 |
White cell and RES disorders | ||
Leucopenia | 1 (0.48) | 1 |
Systemic organ class and preferred terma | Total (N = 209) | |||
---|---|---|---|---|
Adverse Event | Adverse Drug Reaction | |||
Number of Subjects (%) | Number of Events | Number of Subjects (%) | Number of Events | |
Total | 113 (54.07) | 211 | 90 (43.06) | 156 |
Resistance mechanism disorders | 48 (22.97) | 66 | 35 (16.75) | 50 |
Pharyngitis | 24 (11.48) | 32 | 23 (11.00) | 31 |
Upper respiratory tract infection | 10 (4.78) | 15 | 5 (2.39) | 10 |
Urinary tract infection | 4 (1.91) | 4 | 1 (0.48) | 1 |
Rhinitis | 3 (1.44) | 3 | 0 (0.00) | 0 |
Pneumonia | 3 (1.44) | 3 | 2 (0.96) | 2 |
Herpes simplex | 2 (0.96) | 2 | 2 (0.96) | 2 |
Cystitis | 2 (0.96) | 2 | 1 (0.48) | 1 |
Infection susceptibility increased | 1 (0.48) | 1 | 1 (0.48) | 1 |
Abscess | 1 (0.48) | 1 | 0 (0.00) | 0 |
Herpes zoster | 1 (0.48) | 1 | 1 (0.48) | 1 |
Dermatitis fungal | 1 (0.48) | 1 | 1 (0.48) | 1 |
Polyomavirus infection | 1 (0.48) | 1 | 0 (0.00) | 0 |
Gastro-intestinal system disorders | 39 (18.66) | 49 | 34 (16.27) | 38 |
Diarrhoea | 12 (5.74) | 13 | 11 (5.26) | 11 |
Stomatitis | 7 (3.35) | 7 | 7 (3.35) | 7 |
Stomatitis ulcerative | 7 (3.35) | 7 | 7 (3.35) | 7 |
Abdominal pain | 4 (1.91) | 4 | 4 (1.91) | 4 |
Gastritis | 3 (1.44) | 3 | 2 (0.96) | 2 |
Constipation | 2 (0.96) | 2 | 1 (0.48) | 1 |
Dyspepsia | 2 (0.96) | 3 | 2 (0.96) | 3 |
Nausea | 2 (0.96) | 2 | 1 (0.48) | 1 |
Enteritis | 2 (0.96) | 2 | 1 (0.48) | 1 |
Vomiting | 1 (0.48) | 2 | 0 (0.00) | 0 |
Ileus | 1 (0.48) | 2 | 0 (0.00) | 0 |
Tooth caries | 1 (0.48) | 1 | 0 (0.00) | 0 |
Periodontal destruction | 1 (0.48) | 1 | 1 (0.48) | 1 |
Urinary system disorders | 15 (7.18) | 16 | 11 (5.26) | 11 |
Azotaemia | 10 (4.78) | 10 | 7 (3.35) | 7 |
Albuminuria | 2 (0.96) | 2 | 2 (0.96) | 2 |
Nephropathy toxic | 1 (0.48) | 1 | 0 (0.00) | 0 |
Urinary tract disorder | 1 (0.48) | 1 | 0 (0.00) | 0 |
Oliguria | 1 (0.48) | 1 | 1 (0.48) | 1 |
Renal artery occlusion | 1 (0.48) | 1 | 1 (0.48) | 1 |
Skin and appendages disorders | 15 (7.18) | 17 | 13 (6.22) | 14 |
Acne | 5 (2.39) | 5 | 5 (2.39) | 5 |
Rash | 4 (1.91) | 4 | 4 (1.91) | 4 |
Onychomycosis | 2 (0.96) | 2 | 1 (0.48) | 1 |
Rash erythematous | 2 (0.96) | 2 | 2 (0.96) | 2 |
Folliculitis | 1 (0.48) | 1 | 0 (0.00) | 0 |
Eczema | 1 (0.48) | 1 | 1 (0.48) | 1 |
Dermatitis contact | 1 (0.48) | 1 | 0 (0.00) | 0 |
Dermatitis | 1 (0.48) | 1 | 1 (0.48) | 1 |
Metabolic and nutritional disorders | 13 (6.22) | 14 | 11 (5.26) | 12 |
Diabetes mellitus | 3 (1.44) | 3 | 3 (1.44) | 3 |
Hyperlipemia | 4 (1.91) | 4 | 4 (1.91) | 4 |
Hyperkalemia | 2 (0.96) | 2 | 2 (0.96) | 2 |
Diabetes mellitus aggravated | 2 (0.96) | 2 | 2 (0.96) | 2 |
Hyperphosphatemia | 1 (0.48) | 1 | 0 (0.00) | 0 |
Glycosuria | 1 (0.48) | 1 | 1 (0.48) | 1 |
Plasma osmolality increased | 1 (0.48) | 1 | 0 (0.00) | 0 |
Body as a whole– general disorders | 11 (5.26) | 11 | 8 (3.83) | 8 |
Edema peripheral | 2 (0.96) | 2 | 2 (0.96) | 2 |
Face edema | 2 (0.96) | 2 | 2 (0.96) | 2 |
Fever | 2 (0.96) | 2 | 1 (0.48) | 1 |
Allergic reaction | 1 (0.48) | 1 | 1 (0.48) | 1 |
Leg pain | 1 (0.48) | 1 | 0 (0.00) | 0 |
Ascites | 1 (0.48) | 1 | 0 (0.00) | 0 |
Anaphylactic reaction | 1 (0.48) | 1 | 1 (0.48) | 1 |
Fatigue | 1 (0.48) | 1 | 1 (0.48) | 1 |
Liver and biliary system disorders | 6 (2.87) | 7 | 3 (1.44) | 4 |
SGOT increased | 2 (0.96) | 2 | 1 (0.48) | 1 |
Hepatic enzymes increased | 2 (0.96) | 2 | 0 (0.00) | 0 |
SGPT increased | 1 (0.48) | 1 | 1 (0.48) | 1 |
Hepatic function abnormal | 1 (0.48) | 1 | 1 (0.48) | 1 |
Cholangitis | 1 (0.48) | 1 | 1 (0.48) | 1 |
Musculo-skeletal system disorders | 6 (2.87) | 6 | 4 (1.91) | 4 |
Osteoporosis | 2 (0.96) | 2 | 2 (0.96) | 2 |
Fracture | 2 (0.96) | 2 | 0 (0.00) | 0 |
Myalgia | 1 (0.48) | 1 | 1 (0.48) | 1 |
Avascular necrosis bone | 1 (0.48) | 1 | 1 (0.48) | 1 |
Secondary terms – events | 6 (2.87) | 6 | 3 (1.44) | 3 |
Transplant rejection | 6 (2.87) | 6 | 3 (1.44) | 3 |
Respiratory system disorders | 4 (1.91) | 4 | 3 (1.44) | 3 |
Coughing | 3 (1.44) | 3 | 3 (1.44) | 3 |
Dysonoea | 1 (0.48) | 1 | 0 (0.00) | 0 |
White cell and RES disorders | 3 (1.44) | 3 | 2 (0.96) | 2 |
Leucopenia | 2 (0.96) | 2 | 2 (0.96) | 2 |
Granulocyopenia | 1 (0.48) | 1 | 0 (0.00) | 0 |
Central & peripheral nervous system disorders | 3 (1.44) | 4 | 2 (0.96) | 3 |
Headache | 2 (0.96) | 2 | 1 (0.48) | 1 |
Hypoaesthesia | 1 (0.48) | 1 | 1 (0.48) | 1 |
Tremor | 1 (0.48) | 1 | 1 (0.48) | 1 |
Red blood cell disorders | 2 (0.96) | 2 | 2 (0.96) | 2 |
Anaemia | 1 (0.48) | 1 | 1 (0.48) | 1 |
Polycythaemia | 1 (0.48) | 1 | 1 (0.48) | 1 |
Endocrine disorders | 1 (0.48) | 1 | 0 (0.00) | 0 |
Hyperparathyroidism | 1 (0.48) | 1 | 0 (0.00) | 0 |
Vision disorders | 1 (0.48) | 1 | 1 (0.48) | 1 |
Meibomianitis | 1 (0.48) | 1 | 1 (0.48) | 1 |
Myo-, endo-, pericardial & valve disorders | 1 (0.48) | 1 | 0 (0.00) | 0 |
Angina pectoris aggravated | 1 (0.48) | 1 | 0 (0.00) | 0 |
Cardiovascular disorders, general | 1 (0.48) | 1 | 0 (0.00) | 0 |
Hypertension | 1 (0.48) | 1 | 0 (0.00) | 0 |
Psychiatric disorders | 1 (0.48) | 1 | 1 (0.48) | 1 |
Insomnia | 1 (0.48) | 1 | 1 (0.48) | 1 |
Platelet, bleeding & clotting disorders | 1 (0.48) | 1 | 0 (0.00) | 0 |
Thrombocytopenia | 1 (0.48) | 1 | 0 (0.00) | 0 |
Systemic organ class and preferred terma | Total (N = 209) | |||
---|---|---|---|---|
SAEs | SADRs | |||
Number of Subjects (%) | Number of Events | Number of Subjects (%) | Number of Events | |
Total | 16 (7.66) | 28 | 6 (2.87) | 9 |
Resistance mechanism disorders | 6 (2.87) | 7 | 3 (1.44) | 3 |
Pneumonia | 2 (0.96) | 2 | 1 (0.48) | 1 |
Cystitis | 1 (0.48) | 1 | 0 (0.00) | 0 |
Infection susceptibility increased | 1 (0.48) | 1 | 1 (0.48) | 1 |
Abscess | 1 (0.48) | 1 | 0 (0.00) | 0 |
Herpes zoster | 1 (0.48) | 1 | 1 (0.48) | 1 |
Polyomavirus infection | 1 (0.48) | 1 | 0 (0.00) | 0 |
Gastro-intestinal system disorders | 3 (1.44) | 4 | 2 (0.96) | 2 |
Diarrhea | 2 (0.96) | 2 | 2 (0.96) | 2 |
Ileus | 1 (0.48) | 2 | 0 (0.00) | 0 |
Urinary system disorders | 5 (2.39) | 5 | 3 (1.44) | 3 |
Azotemia | 4 (1.91) | 4 | 3 (1.44) | 3 |
Urinary tract disorder | 1 (0.48) | 1 | 0 (0.00) | 0 |
Skin and appendages disorders | 1 (0.48) | 1 | 0 (0.00) | 0 |
Dermatitis contact | 1 (0.48) | 1 | 0 (0.00) | 0 |
Metabolic and nutritional disorders | 1 (0.48) | 1 | 0 (0.00) | 0 |
Plasma osmolality increased | 1 (0.48) | 1 | 0 (0.00) | 0 |
Body as a whole– general disorders | 1 (0.48) | 1 | 0 (0.00) | 0 |
Ascites | 1 (0.48) | 1 | 0 (0.00) | 0 |
Liver and biliary system disorders | 1 (0.48) | 1 | 1 (0.48) | 1 |
Cholangitis | 1 (0.48) | 1 | 1 (0.48) | 1 |
Musculo-skeletal system disorders | 1 (0.48) | 1 | 0 (0.00) | 0 |
Fracture | 1 (0.48) | 1 | 0 (0.00) | 0 |
Secondary terms – events | 2 (0.96) | 2 | 0 (0.00) | 0 |
Transplant rejection | 2 (0.96) | 2 | 0 (0.00) | 0 |
Respiratory system disorders | 1 (0.48) | 1 | 0 (0.00) | 0 |
Dyspnea | 1 (0.48) | 1 | 0 (0.00) | 0 |
White cell and RES disorders | 1 (0.48) | 1 | 0 (0.00) | 0 |
Granulocyopenia | 1 (0.48) | 1 | 0 (0.00) | 0 |
Endocrine disorders | 1 (0.48) | 1 | 0 (0.00) | 0 |
Hyperparathyroidism | 1 (0.48) | 1 | 0 (0.00) | 0 |
Myo-, endo-, pericardial & valve disorders | 1 (0.48) | 1 | 0 (0.00) | 0 |
Angina pectoris aggravated | 1 (0.48) | 1 | 0 (0.00) | 0 |
Cardiovascular disorders, general | 1 (0.48) | 1 | 0 (0.00) | 0 |
Hypertension | 1 (0.48) | 1 | 0 (0.00) | 0 |
Efficacy
Total (N = 209) | |||
---|---|---|---|
Yes, n (%) | 95% CI (lower, upper) | Total, n (%) | |
Acute rejection | 6 (2.87) | 0.91, 5.79 | 209 (100.00) |
Patient survivala | 205 (99.51) | 98.57, 100.00 | 206 (98.56) |
Graft survivala | 205 (99.51) | 98.57, 100.00 | 206 (98.56) |
Graft functionb | |||
eGFR (mL/min) | 64.72 ± 19.56c | 182 (87.08) |