Trial Outcomes & Findings for Efficacy and Safety of Everolimus With Enteric-Coated Mycophenolate Sodium (EC-MPS) in a Cyclosporine Microemulsion-free Regimen Compared to Standard Therapy in de Novo Renal Transplant Patients (NCT NCT00154310)

Last Updated: 2013-11-13

Results Overview

Renal function at the end of the trial assessed as mean absolute values of the glomerular filtration rate (GFR) calculated by Nankivell formula 12 months after renal transplantation. The Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)\^2 + C ; where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. Estimated GFR is expressed in mL/min per 1.73m\^2.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

300 participants

Primary outcome timeframe

at Month 12 post transplantation

Results posted on

2013-11-13

Participant Flow

This study was an open-label, randomized, parallel-group, multi-center study with two treatment groups, cyclosporine continuation and cyclosporine withdrawal starting from Month 4.5 post-transplant. Study started in June 2005 and ended in September 2008.

Participant milestones

Participant milestones
Measure	Everolimus + Mycophenolate Sodium Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.	Cyclosporine + Mycophenolate Sodium Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
Overall Study STARTED	155	145
Overall Study COMPLETED	118	117
Overall Study NOT COMPLETED	37	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus + Mycophenolate Sodium Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.	Cyclosporine + Mycophenolate Sodium Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
Overall Study Adverse Event	19	9
Overall Study Lack of Efficacy	5	4
Overall Study Protocol Violation	4	2
Overall Study Withdrawal by Subject	9	3
Overall Study Lost to Follow-up	0	8
Overall Study Administrative problems	0	1
Overall Study Death	0	1

Baseline Characteristics

Efficacy and Safety of Everolimus With Enteric-Coated Mycophenolate Sodium (EC-MPS) in a Cyclosporine Microemulsion-free Regimen Compared to Standard Therapy in de Novo Renal Transplant Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus + Mycophenolate Sodium n=155 Participants Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.	Cyclosporine + Mycophenolate Sodium n=145 Participants Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.	Total n=300 Participants Total of all reporting groups
Age Continuous	46.9 Years STANDARD_DEVIATION 11.67 • n=5 Participants	46.7 Years STANDARD_DEVIATION 11.85 • n=7 Participants	46.8 Years STANDARD_DEVIATION 11.73 • n=5 Participants
Sex: Female, Male Female	53 Participants n=5 Participants	59 Participants n=7 Participants	112 Participants n=5 Participants
Sex: Female, Male Male	102 Participants n=5 Participants	86 Participants n=7 Participants	188 Participants n=5 Participants

PRIMARY outcome

Timeframe: at Month 12 post transplantation

Population: Intent to Treat Population (randomized patients); Last Observation Carried Forward (LOCF). One patient in

Outcome measures

Outcome measures
Measure	Everolimus + Mycophenolate Sodium n=154 Participants Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.	Cyclosporine + Mycophenolate Sodium n=145 Participants Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
Renal Function (Nankivell Formula) at Month 12 Post Transplantation.	71.84 mL/min /1.73m^2 Standard Deviation 18.53	61.24 mL/min /1.73m^2 Standard Deviation 16.65

SECONDARY outcome

Timeframe: Up to Month 12

Population: Intent to Treat Population (Randomized Patients)

The number of participants with occurrence of biopsy proven acute rejection (BPAR), graft loss, or death up to Month 12 during the randomized treatment period. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III according to Banff 97 classification. A graft core biopsy was performed prior to 24 hours following initiation of graft rejection therapy. The allograft is presumed to be lost on the day the patient starts dialysis and was not able to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was the day of graft loss.

Outcome measures

Outcome measures
Measure	Everolimus + Mycophenolate Sodium n=154 Participants Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.	Cyclosporine + Mycophenolate Sodium n=146 Participants Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death BPAR: Yes	15 Participants	5 Participants
Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death BPAR: No	139 Participants	141 Participants
Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death Graft Loss: Yes	0 Participants	0 Participants
Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death Graft Loss: No	154 Participants	146 Participants
Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death Death: Yes	0 Participants	1 Participants
Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death Death: No	154 Participants	145 Participants

SECONDARY outcome

Timeframe: up to or at Month 12

Population: Intention to treat (ITT) population (Randomized Patients).

Treatment failures defined as a composite endpoint of biopsy proven acute rejection, graft loss, death, loss to follow up and discontinuations due to lack of efficacy or toxicity, or conversion to another regimen (at least one condition must be present).

Outcome measures

Outcome measures
Measure	Everolimus + Mycophenolate Sodium n=154 Participants Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.	Cyclosporine + Mycophenolate Sodium n=146 Participants Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
Number of Participants With Occurrence of Treatment Failures Treatment failure: Yes	29 Participants	23 Participants
Number of Participants With Occurrence of Treatment Failures Treatment failure: No	125 Participants	123 Participants

SECONDARY outcome

Timeframe: Month 4.5 and Month 12

Population: Safety Population for whom data was available at Month 4.5 and end of treatment.

An updated 1991 Framingham coronary prediction algorithm was used to estimate the total risk of developing coronary heart diseases (CHD) over the course of 10 years. Risk was calculated separately for male and females. To calculate risk, points were assigned for each of the following risk factors: age, levels of LDL cholesterol, HDL cholesterol, blood pressure, cigarette smoking, and diabetes mellitus. The sum of the individual risk factor points gives a total point score, which ranges from -5 to 18 for men and -16 to 24 for women. Higher points indicate a higher risk for CHD.

Outcome measures

Outcome measures
Measure	Everolimus + Mycophenolate Sodium n=155 Participants Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.	Cyclosporine + Mycophenolate Sodium n=145 Participants Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
Changes in Cardiovascular Risk From Month 4.5 to Final Assessment at Month 12 Male (n= 55, 37)	0.5 Points Standard Deviation 1.87	0.1 Points Standard Deviation 1.86
Changes in Cardiovascular Risk From Month 4.5 to Final Assessment at Month 12 Female (n= 22, 35)	0.0 Points Standard Deviation 2.01	0.8 Points Standard Deviation 2.70
Changes in Cardiovascular Risk From Month 4.5 to Final Assessment at Month 12 Total Population (n= 77, 72)	0.4 Points Standard Deviation 1.91	0.4 Points Standard Deviation 2.32

SECONDARY outcome

Timeframe: Aes from end of core study period (month 12) to end of follow-up period (month 60)

Population: Safety Population consisted of all participants in whom transplantation was performed and who were treated with at least one dose of any immunosuppressive medication.

Additional information about the number of participants who experienced Adverse Events (greater than 5%) or Serious Adverse Events can be found in the Adverse Event section.

Outcome measures

Outcome measures
Measure	Everolimus + Mycophenolate Sodium n=155 Participants Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.	Cyclosporine + Mycophenolate Sodium n=145 Participants Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
Number of Participants Who Experienced an Adverse Event or Serious Adverse Event Adverse Events	155 Participants	145 Participants
Number of Participants Who Experienced an Adverse Event or Serious Adverse Event Serious Adverse Events	95 Participants	86 Participants

Adverse Events

Certican

Serious events: 103 serious events

Other events: 155 other events

Deaths: 0 deaths

Sandimmun Optoral

Serious events: 93 serious events

Other events: 145 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Certican n=155 participants at risk Certican	Sandimmun Optoral n=145 participants at risk Sandimmun Optoral
Blood and lymphatic system disorders Hypochromic anaemia	0.65% 1/155	0.00% 0/145
Blood and lymphatic system disorders Leukocytosis	0.00% 0/155	0.69% 1/145
Blood and lymphatic system disorders Leukopenia	0.00% 0/155	0.69% 1/145
Blood and lymphatic system disorders Thrombocytopenia	0.65% 1/155	0.00% 0/145
Cardiac disorders Acute coronary syndrome	0.65% 1/155	0.00% 0/145
Cardiac disorders Arrhythmia	0.00% 0/155	0.69% 1/145
Cardiac disorders Atrial fibrillation	1.3% 2/155	0.00% 0/145
Cardiac disorders Cardiac arrest	0.65% 1/155	0.00% 0/145
Cardiac disorders Cardiac failure chronic	0.65% 1/155	0.00% 0/145
Cardiac disorders Coronary artery disease	0.65% 1/155	1.4% 2/145
Cardiac disorders Myocardial infarction	1.9% 3/155	0.69% 1/145
Cardiac disorders Myopericarditis	0.65% 1/155	0.00% 0/145
Cardiac disorders Supraventricular tachycardia	0.65% 1/155	0.00% 0/145
Cardiac disorders Ventricular tachycardia	0.65% 1/155	0.69% 1/145
Congenital, familial and genetic disorders Congenital cystic kidney disease	0.65% 1/155	0.69% 1/145
Congenital, familial and genetic disorders Pyloric stenosis	0.00% 0/155	0.69% 1/145
Ear and labyrinth disorders Deafness	0.65% 1/155	0.00% 0/145
Ear and labyrinth disorders Tinnitus	0.65% 1/155	0.00% 0/145
Endocrine disorders Hyperparathyroidism	0.00% 0/155	0.69% 1/145
Endocrine disorders Hyperparathyroidism secondary	0.65% 1/155	0.69% 1/145
Eye disorders Amaurosis fugax	0.00% 0/155	0.69% 1/145
Gastrointestinal disorders Abdominal pain	0.00% 0/155	0.69% 1/145
Gastrointestinal disorders Colitis	1.3% 2/155	0.00% 0/145
Gastrointestinal disorders Constipation	0.65% 1/155	0.00% 0/145
Gastrointestinal disorders Diarrhoea	3.9% 6/155	2.8% 4/145
Gastrointestinal disorders Enteritis	1.3% 2/155	0.69% 1/145
Gastrointestinal disorders Gastric polyps	0.00% 0/155	0.69% 1/145
Gastrointestinal disorders Gastritis erosive	0.65% 1/155	0.00% 0/145
Gastrointestinal disorders Inguinal hernia	0.00% 0/155	0.69% 1/145
Gastrointestinal disorders Nausea	0.00% 0/155	0.69% 1/145
Gastrointestinal disorders Periodontitis	0.65% 1/155	0.00% 0/145
Gastrointestinal disorders Peritoneal fibrosis	0.00% 0/155	0.69% 1/145
Gastrointestinal disorders Peritoneal haemorrhage	0.65% 1/155	0.00% 0/145
Gastrointestinal disorders Peritonitis	0.00% 0/155	0.69% 1/145
Gastrointestinal disorders Retroperitoneal haematoma	0.00% 0/155	0.69% 1/145
Gastrointestinal disorders Small intestinal perforation	0.65% 1/155	0.00% 0/145
Gastrointestinal disorders Subileus	0.00% 0/155	0.69% 1/145
Gastrointestinal disorders Vomiting	0.65% 1/155	0.69% 1/145
General disorders Catheter site haematoma	0.00% 0/155	0.69% 1/145
General disorders Fat necrosis	0.00% 0/155	0.69% 1/145
General disorders Generalised oedema	0.65% 1/155	0.00% 0/145
General disorders Hernia	0.00% 0/155	1.4% 2/145
General disorders Hernia obstructive	0.65% 1/155	0.00% 0/145
General disorders Impaired healing	0.00% 0/155	0.69% 1/145
General disorders Non-cardiac chest pain	0.00% 0/155	0.69% 1/145
General disorders Oedema peripheral	0.00% 0/155	1.4% 2/145
General disorders Pyrexia	3.2% 5/155	0.69% 1/145
Hepatobiliary disorders Hydrocholecystis	0.00% 0/155	0.69% 1/145
Immune system disorders Transplant rejection	0.00% 0/155	0.69% 1/145
Infections and infestations Aspergilloma	0.65% 1/155	0.00% 0/145
Infections and infestations Bacterial infection	0.00% 0/155	0.69% 1/145
Infections and infestations Bronchitis	1.3% 2/155	0.00% 0/145
Infections and infestations Bronchopulmonary aspergillosis	0.65% 1/155	0.00% 0/145
Infections and infestations Chronic sinusitis	0.00% 0/155	0.69% 1/145
Infections and infestations Cystitis	0.65% 1/155	0.00% 0/145
Infections and infestations Cytomegalovirus infection	3.9% 6/155	3.4% 5/145
Infections and infestations Diverticulitis	0.65% 1/155	0.00% 0/145
Infections and infestations Endocarditis	0.65% 1/155	0.00% 0/145
Infections and infestations Enterococcal infection	0.00% 0/155	0.69% 1/145
Infections and infestations Erysipelas	0.00% 0/155	1.4% 2/145
Infections and infestations Febrile infection	0.65% 1/155	0.00% 0/145
Infections and infestations Gastroenteritis	4.5% 7/155	2.8% 4/145
Infections and infestations Gastroenteritis salmonella	0.65% 1/155	0.00% 0/145
Infections and infestations Gastroenteritis viral	0.65% 1/155	0.00% 0/145
Infections and infestations Gastrointestinal infection	1.3% 2/155	0.69% 1/145
Infections and infestations Herpes zoster	0.00% 0/155	2.1% 3/145
Infections and infestations Human polyomavirus infection	0.00% 0/155	0.69% 1/145
Infections and infestations Infected lymphocele	0.00% 0/155	0.69% 1/145
Infections and infestations Infection	1.3% 2/155	0.69% 1/145
Infections and infestations Lung infection	0.65% 1/155	0.00% 0/145
Infections and infestations Nasopharyngitis	0.65% 1/155	0.00% 0/145
Infections and infestations Pneumocystis jiroveci pneumonia	1.9% 3/155	1.4% 2/145
Infections and infestations Pneumonia	5.2% 8/155	11.0% 16/145
Infections and infestations Pyelonephritis	2.6% 4/155	2.1% 3/145
Infections and infestations Renal cyst infection	0.65% 1/155	0.69% 1/145
Infections and infestations Respiratory tract infection	0.65% 1/155	0.00% 0/145
Infections and infestations Sepsis	0.65% 1/155	0.69% 1/145
Infections and infestations Shunt infection	0.00% 0/155	1.4% 2/145
Infections and infestations Sinusitis	1.3% 2/155	0.00% 0/145
Infections and infestations Superinfection	0.65% 1/155	0.00% 0/145
Infections and infestations Tracheitis	0.00% 0/155	0.69% 1/145
Infections and infestations Urinary tract infection	11.6% 18/155	9.7% 14/145
Infections and infestations Urosepsis	3.2% 5/155	2.8% 4/145
Infections and infestations Viral upper respiratory tract infection	0.65% 1/155	0.00% 0/145
Infections and infestations Wound infection	0.00% 0/155	0.69% 1/145
Injury, poisoning and procedural complications Abdominal wound dehiscence	0.65% 1/155	0.00% 0/145
Injury, poisoning and procedural complications Anastomotic complication	1.3% 2/155	0.00% 0/145
Injury, poisoning and procedural complications Anastomotic haemorrhage	0.65% 1/155	0.00% 0/145
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	0.00% 0/155	0.69% 1/145
Injury, poisoning and procedural complications Chronic allograft nephropathy	0.65% 1/155	0.00% 0/145
Injury, poisoning and procedural complications Complications of transplanted kidney	1.9% 3/155	4.8% 7/145
Injury, poisoning and procedural complications Fat embolism	0.00% 0/155	0.69% 1/145
Injury, poisoning and procedural complications Femur fracture	0.00% 0/155	0.69% 1/145
Injury, poisoning and procedural complications Foot fracture	0.00% 0/155	0.69% 1/145
Injury, poisoning and procedural complications Incision site haematoma	0.65% 1/155	0.00% 0/145
Injury, poisoning and procedural complications Muscle rupture	0.65% 1/155	0.00% 0/145
Injury, poisoning and procedural complications Operative haemorrhage	0.65% 1/155	0.00% 0/145
Injury, poisoning and procedural complications Perirenal haematoma	0.00% 0/155	0.69% 1/145
Injury, poisoning and procedural complications Post procedural haematoma	0.00% 0/155	0.69% 1/145
Injury, poisoning and procedural complications Post procedural haemorrhage	0.65% 1/155	0.00% 0/145
Injury, poisoning and procedural complications Postoperative hernia	0.00% 0/155	0.69% 1/145
Injury, poisoning and procedural complications Renal haematoma	0.65% 1/155	0.00% 0/145
Injury, poisoning and procedural complications Renal lymphocele	1.3% 2/155	0.00% 0/145
Injury, poisoning and procedural complications Seroma	1.9% 3/155	0.00% 0/145
Injury, poisoning and procedural complications Shunt thrombosis	0.00% 0/155	1.4% 2/145
Injury, poisoning and procedural complications Spinal compression fracture	0.65% 1/155	0.00% 0/145
Injury, poisoning and procedural complications Subcutaneous haematoma	0.00% 0/155	0.69% 1/145
Injury, poisoning and procedural complications Transplant failure	0.65% 1/155	0.69% 1/145
Injury, poisoning and procedural complications Urethral injury	0.65% 1/155	0.00% 0/145
Injury, poisoning and procedural complications Wound dehiscence	0.65% 1/155	2.8% 4/145
Investigations Blood creatinine increased	6.5% 10/155	10.3% 15/145
Investigations Blood urea increased	0.65% 1/155	0.00% 0/145
Investigations Cytomegalovirus test	0.65% 1/155	0.00% 0/145
Investigations Haemoglobin decreased	0.00% 0/155	0.69% 1/145
Investigations Occult blood positive	0.65% 1/155	0.00% 0/145
Investigations Transaminases increased	0.00% 0/155	0.69% 1/145
Metabolism and nutrition disorders Dehydration	0.65% 1/155	2.1% 3/145
Metabolism and nutrition disorders Diabetes mellitus	0.65% 1/155	0.00% 0/145
Metabolism and nutrition disorders Fluid retention	0.65% 1/155	0.00% 0/145
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/155	0.69% 1/145
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/155	0.69% 1/145
Metabolism and nutrition disorders Hyperkalaemia	0.65% 1/155	0.00% 0/145
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/155	0.69% 1/145
Metabolism and nutrition disorders Tetany	0.65% 1/155	0.00% 0/145
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/155	0.69% 1/145
Musculoskeletal and connective tissue disorders Arthropathy	0.00% 0/155	0.69% 1/145
Musculoskeletal and connective tissue disorders Haemarthrosis	0.65% 1/155	0.00% 0/145
Musculoskeletal and connective tissue disorders Myopathy steroid	0.65% 1/155	0.00% 0/145
Musculoskeletal and connective tissue disorders Osteonecrosis	0.65% 1/155	0.69% 1/145
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/155	0.69% 1/145
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/155	0.69% 1/145
Musculoskeletal and connective tissue disorders Synovial cyst	0.65% 1/155	0.00% 0/145
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	1.9% 3/155	1.4% 2/145
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.65% 1/155	0.00% 0/145
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.65% 1/155	0.00% 0/145
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibrous histiocytoma	0.00% 0/155	0.69% 1/145
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Kaposi's sarcoma	0.00% 0/155	0.69% 1/145
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm skin	0.65% 1/155	0.00% 0/145
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parathyroid tumour benign	0.00% 0/155	1.4% 2/145
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/155	0.69% 1/145
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	1.3% 2/155	0.00% 0/145
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	1.3% 2/155	0.00% 0/145
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.00% 0/155	0.69% 1/145
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.65% 1/155	0.00% 0/145
Nervous system disorders Aphasia	0.65% 1/155	0.00% 0/145
Nervous system disorders Cerebrovascular accident	0.65% 1/155	0.00% 0/145
Nervous system disorders Convulsion	0.65% 1/155	0.00% 0/145
Psychiatric disorders Depression	0.65% 1/155	0.69% 1/145
Psychiatric disorders Dysphoria	0.65% 1/155	0.00% 0/145
Psychiatric disorders Psychiatric decompensation	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Focal segmental glomerulosclerosis	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Hydronephrosis	1.9% 3/155	0.00% 0/145
Renal and urinary disorders IgA nephropathy	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Nephritis autoimmune	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Nephropathy	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Nephropathy toxic	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Nephrosclerosis	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Proteinuria	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Renal artery stenosis	1.9% 3/155	0.69% 1/145
Renal and urinary disorders Renal disorder	0.00% 0/155	0.69% 1/145
Renal and urinary disorders Renal failure	0.00% 0/155	0.69% 1/145
Renal and urinary disorders Renal failure acute	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Renal haemorrhage	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Renal impairment	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Renal tubular disorder	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Ureteral necrosis	0.65% 1/155	0.69% 1/145
Renal and urinary disorders Ureteric stenosis	1.9% 3/155	2.1% 3/145
Renal and urinary disorders Urethral discharge	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Urethral perforation	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Urethral stenosis	0.65% 1/155	0.69% 1/145
Renal and urinary disorders Urinary incontinence	0.00% 0/155	0.69% 1/145
Renal and urinary disorders Urinary retention	1.3% 2/155	1.4% 2/145
Renal and urinary disorders Urinary tract disorder	0.65% 1/155	0.00% 0/145
Renal and urinary disorders Urinary tract obstruction	1.3% 2/155	0.00% 0/145
Renal and urinary disorders Urinoma	1.3% 2/155	0.00% 0/145
Renal and urinary disorders Vesicoureteric reflux	0.65% 1/155	0.69% 1/145
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/155	0.69% 1/145
Reproductive system and breast disorders Cervical dysplasia	0.65% 1/155	0.00% 0/145
Reproductive system and breast disorders Ovarian cyst	0.65% 1/155	0.00% 0/145
Reproductive system and breast disorders Pelvic congestion	0.00% 0/155	0.69% 1/145
Reproductive system and breast disorders Postmenopausal haemorrhage	0.65% 1/155	0.00% 0/145
Reproductive system and breast disorders Scrotal oedema	0.00% 0/155	0.69% 1/145
Reproductive system and breast disorders Vaginal haemorrhage	0.65% 1/155	0.00% 0/145
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/155	0.69% 1/145
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.00% 0/155	0.69% 1/145
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/155	1.4% 2/145
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/155	0.69% 1/145
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.00% 0/155	0.69% 1/145
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.9% 3/155	0.69% 1/145
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.65% 1/155	0.00% 0/145
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.65% 1/155	0.69% 1/145
Respiratory, thoracic and mediastinal disorders Stridor	0.00% 0/155	0.69% 1/145
Skin and subcutaneous tissue disorders Erythema nodosum	0.65% 1/155	0.00% 0/145
Skin and subcutaneous tissue disorders Pyoderma gangrenosum	0.00% 0/155	0.69% 1/145
Skin and subcutaneous tissue disorders Rash	0.65% 1/155	0.00% 0/145
Skin and subcutaneous tissue disorders Skin ulcer	0.65% 1/155	0.00% 0/145
Surgical and medical procedures Kidney anastomosis	0.00% 0/155	0.69% 1/145
Vascular disorders Arterial restenosis	0.00% 0/155	0.69% 1/145
Vascular disorders Deep vein thrombosis	1.3% 2/155	0.00% 0/145
Vascular disorders Haematoma	1.9% 3/155	1.4% 2/145
Vascular disorders Haemorrhage	1.3% 2/155	0.00% 0/145
Vascular disorders Hypertension	1.3% 2/155	0.00% 0/145
Vascular disorders Hypertensive crisis	1.3% 2/155	0.00% 0/145
Vascular disorders Hypotension	0.00% 0/155	0.69% 1/145
Vascular disorders Lymphocele	5.8% 9/155	9.7% 14/145
Vascular disorders Peripheral artery aneurysm	0.65% 1/155	0.00% 0/145
Vascular disorders Shock haemorrhagic	1.3% 2/155	0.00% 0/145
Vascular disorders Thrombosis	0.00% 0/155	0.69% 1/145
Vascular disorders Venous thrombosis	0.65% 1/155	0.00% 0/145
Vascular disorders Venous thrombosis limb	0.65% 1/155	0.00% 0/145

Other adverse events

Other adverse events
Measure	Certican n=155 participants at risk Certican	Sandimmun Optoral n=145 participants at risk Sandimmun Optoral
Blood and lymphatic system disorders Anaemia	27.7% 43/155	24.1% 35/145
Blood and lymphatic system disorders Leukocytosis	11.0% 17/155	15.2% 22/145
Blood and lymphatic system disorders Leukopenia	15.5% 24/155	16.6% 24/145
Blood and lymphatic system disorders Thrombocytopenia	11.6% 18/155	3.4% 5/145
Ear and labyrinth disorders Vertigo	4.5% 7/155	6.2% 9/145
Gastrointestinal disorders Abdominal pain	12.9% 20/155	9.7% 14/145
Gastrointestinal disorders Abdominal pain upper	7.7% 12/155	8.3% 12/145
Gastrointestinal disorders Aphthous stomatitis	14.2% 22/155	2.1% 3/145
Gastrointestinal disorders Constipation	52.9% 82/155	49.7% 72/145
Gastrointestinal disorders Diarrhoea	38.7% 60/155	29.0% 42/145
Gastrointestinal disorders Dyspepsia	9.7% 15/155	7.6% 11/145
Gastrointestinal disorders Flatulence	16.1% 25/155	13.8% 20/145
Gastrointestinal disorders Nausea	41.3% 64/155	40.7% 59/145
Gastrointestinal disorders Vomiting	24.5% 38/155	22.1% 32/145
General disorders Asthenia	1.3% 2/155	6.2% 9/145
General disorders Fatigue	4.5% 7/155	6.9% 10/145
General disorders Impaired healing	5.2% 8/155	3.4% 5/145
General disorders Oedema	28.4% 44/155	23.4% 34/145
General disorders Oedema peripheral	24.5% 38/155	22.1% 32/145
General disorders Pain	19.4% 30/155	17.9% 26/145
General disorders Pyrexia	15.5% 24/155	15.2% 22/145
Infections and infestations Bronchitis	10.3% 16/155	4.8% 7/145
Infections and infestations Cytomegalovirus infection	16.8% 26/155	16.6% 24/145
Infections and infestations Gastroenteritis	9.7% 15/155	11.7% 17/145
Infections and infestations Gastrointestinal infection	6.5% 10/155	4.8% 7/145
Infections and infestations Herpes zoster	5.2% 8/155	6.9% 10/145
Infections and infestations Human polyomavirus infection	5.2% 8/155	2.1% 3/145
Infections and infestations Infection	5.8% 9/155	6.2% 9/145
Infections and infestations Nasopharyngitis	31.6% 49/155	30.3% 44/145
Infections and infestations Oral herpes	7.1% 11/155	0.69% 1/145
Infections and infestations Pneumonia	10.3% 16/155	6.2% 9/145
Infections and infestations Respiratory tract infection	7.7% 12/155	8.3% 12/145
Infections and infestations Rhinitis	7.7% 12/155	5.5% 8/145
Infections and infestations Upper respiratory tract infection	7.7% 12/155	4.8% 7/145
Infections and infestations Urinary tract infection	58.1% 90/155	57.2% 83/145
Infections and infestations Wound infection	2.6% 4/155	7.6% 11/145
Injury, poisoning and procedural complications Complications of transplanted kidney	13.5% 21/155	16.6% 24/145
Injury, poisoning and procedural complications Procedural pain	32.3% 50/155	33.1% 48/145
Injury, poisoning and procedural complications Wound complication	32.9% 51/155	31.7% 46/145
Injury, poisoning and procedural complications Wound dehiscence	3.9% 6/155	5.5% 8/145
Investigations Blood creatinine increased	32.9% 51/155	33.8% 49/145
Investigations C-reactive protein increased	4.5% 7/155	5.5% 8/145
Investigations Weight increased	5.2% 8/155	9.7% 14/145
Metabolism and nutrition disorders Diabetes mellitus	12.3% 19/155	8.3% 12/145
Metabolism and nutrition disorders Fluid retention	3.9% 6/155	8.3% 12/145
Metabolism and nutrition disorders Hypercalcaemia	9.7% 15/155	17.2% 25/145
Metabolism and nutrition disorders Hypercholesterolaemia	29.0% 45/155	28.3% 41/145
Metabolism and nutrition disorders Hyperglycaemia	15.5% 24/155	11.0% 16/145
Metabolism and nutrition disorders Hyperkalaemia	11.6% 18/155	14.5% 21/145
Metabolism and nutrition disorders Hyperlipidaemia	14.8% 23/155	11.0% 16/145
Metabolism and nutrition disorders Hyperphosphataemia	7.1% 11/155	8.3% 12/145
Metabolism and nutrition disorders Hypertriglyceridaemia	7.1% 11/155	3.4% 5/145
Metabolism and nutrition disorders Hyperuricaemia	6.5% 10/155	13.8% 20/145
Metabolism and nutrition disorders Hypocalcaemia	14.8% 23/155	18.6% 27/145
Metabolism and nutrition disorders Hypokalaemia	29.0% 45/155	24.8% 36/145
Metabolism and nutrition disorders Hypomagnesaemia	5.2% 8/155	9.0% 13/145
Metabolism and nutrition disorders Hyponatraemia	3.9% 6/155	6.9% 10/145
Metabolism and nutrition disorders Hypophosphataemia	30.3% 47/155	29.7% 43/145
Metabolism and nutrition disorders Hypoproteinaemia	5.2% 8/155	7.6% 11/145
Metabolism and nutrition disorders Iron deficiency	1.9% 3/155	5.5% 8/145
Metabolism and nutrition disorders Metabolic acidosis	9.7% 15/155	6.9% 10/145
Musculoskeletal and connective tissue disorders Arthralgia	10.3% 16/155	8.3% 12/145
Musculoskeletal and connective tissue disorders Back pain	16.8% 26/155	10.3% 15/145
Musculoskeletal and connective tissue disorders Muscle spasms	5.8% 9/155	6.9% 10/145
Musculoskeletal and connective tissue disorders Myalgia	6.5% 10/155	2.8% 4/145
Musculoskeletal and connective tissue disorders Pain in extremity	9.0% 14/155	3.4% 5/145
Nervous system disorders Headache	16.1% 25/155	14.5% 21/145
Nervous system disorders Tremor	6.5% 10/155	6.2% 9/145
Psychiatric disorders Insomnia	22.6% 35/155	22.1% 32/145
Psychiatric disorders Sleep disorder	13.5% 21/155	13.8% 20/145
Renal and urinary disorders Bladder pain	5.2% 8/155	7.6% 11/145
Renal and urinary disorders Dysuria	4.5% 7/155	6.2% 9/145
Renal and urinary disorders Haematuria	18.1% 28/155	21.4% 31/145
Renal and urinary disorders Leukocyturia	14.2% 22/155	12.4% 18/145
Renal and urinary disorders Polyuria	6.5% 10/155	11.0% 16/145
Renal and urinary disorders Proteinuria	16.1% 25/155	17.2% 25/145
Renal and urinary disorders Urinary retention	7.1% 11/155	2.8% 4/145
Respiratory, thoracic and mediastinal disorders Cough	16.8% 26/155	20.0% 29/145
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.3% 19/155	11.7% 17/145
Skin and subcutaneous tissue disorders Acne	9.0% 14/155	7.6% 11/145
Skin and subcutaneous tissue disorders Hypertrichosis	3.2% 5/155	5.5% 8/145
Skin and subcutaneous tissue disorders Rash	5.2% 8/155	2.8% 4/145
Vascular disorders Haematoma	5.2% 8/155	5.5% 8/145
Vascular disorders Hypertension	11.0% 17/155	15.2% 22/145
Vascular disorders Hypotension	14.2% 22/155	22.1% 32/145
Vascular disorders Lymphocele	11.0% 17/155	15.9% 23/145

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER