Trial Outcomes & Findings for Steroid Withdrawal and Donor-specific Anti-HLA Antibodies in Renal Transplant Patients (NCT NCT02284464)

NCT ID: NCT02284464

Last Updated: 2020-04-14

Results Overview

Measurements of DSA at baseline, and at 3, 6, 12, 18 and 24 months

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 230 participants
• Primary outcome timeframe: 24 months
• Results posted on: 2020-04-14

Participant Flow

Of the 230 patients, 125 were not randomized because of: screening failure 74; patient wishes 16; acute rejection 9; graft loss 9; died 3; lost to follow-up 1 and other causes 13. The main causes of screening failure were: creatinine >2 mg/dl and subclinical rejection in the protocol biopsy at the third month. 105 patients were finally included

Participant milestones

Measure	Steroids, Tacrolimus and Mycophenolate Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Overall Study STARTED	52	53
Overall Study COMPLETED	39	36
Overall Study NOT COMPLETED	13	17

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Steroid Withdrawal and Donor-specific Anti-HLA Antibodies in Renal Transplant Patients

Baseline characteristics by cohort

Measure	Steroids, Tacrolimus and Mycophenolate n=52 Participants Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=53 Participants Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids	Total n=105 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	43 Participants n=5 Participants	44 Participants n=7 Participants	87 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Age, Continuous	54.8 years STANDARD_DEVIATION 10 • n=5 Participants	52.1 years STANDARD_DEVIATION 14 • n=7 Participants	53.4 years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	38 Participants n=7 Participants	77 Participants n=5 Participants
Race/Ethnicity, Customized Race / Ethnicity · Caucasian	47 Participants n=5 Participants	51 Participants n=7 Participants	98 Participants n=5 Participants
Race/Ethnicity, Customized Race / Ethnicity · Black	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race / Ethnicity · North African	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race / Ethnicity · Hispanic	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Spain	52 participants n=5 Participants	53 participants n=7 Participants	105 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 months

Measurements of DSA at baseline, and at 3, 6, 12, 18 and 24 months

Outcome measures

Measure	Steroids, Tacrolimus and Mycophenolate n=39 Participants Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=36 Participants Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Cases of Kidney Transplant Patients With DSA	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 24 months

Measurement at 24 months according to the Banff classification. The Banff Classification of Allograft Pathology is an international consensus classification for the reporting of biopsies from solid organ transplant. The scale ranges from 0 to 3, 3 being the worst.

Outcome measures

Measure	Steroids, Tacrolimus and Mycophenolate n=28 Participants Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=26 Participants Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Mean Score on the Protocol Biopsies in the Two Treatment Groups Interstitial fibrosis and tubular atrophy	1.18 score on a scale Standard Deviation 1.14	1.83 score on a scale Standard Deviation 1.5
Mean Score on the Protocol Biopsies in the Two Treatment Groups Chronic graft lesion	1.96 score on a scale Standard Deviation 1.5	2.6 score on a scale Standard Deviation 1.5
Mean Score on the Protocol Biopsies in the Two Treatment Groups Glomerulitis	0.17 score on a scale Standard Deviation 0.4	0.08 score on a scale Standard Deviation 0.3
Mean Score on the Protocol Biopsies in the Two Treatment Groups Peritubular capillaritis	0.24 score on a scale Standard Deviation 0.6	0.20 score on a scale Standard Deviation 0.5
Mean Score on the Protocol Biopsies in the Two Treatment Groups Tubulitis	0.5 score on a scale Standard Deviation 0.7	0.56 score on a scale Standard Deviation 0.6
Mean Score on the Protocol Biopsies in the Two Treatment Groups Interstitial inflammation	0.82 score on a scale Standard Deviation 0.7	0.68 score on a scale Standard Deviation 0.7
Mean Score on the Protocol Biopsies in the Two Treatment Groups Arteritis	0 score on a scale Standard Deviation 0	0 score on a scale Standard Deviation 0
Mean Score on the Protocol Biopsies in the Two Treatment Groups Interstitial fibrosis	0.6 score on a scale Standard Deviation 0.62	0.88 score on a scale Standard Deviation 0.78
Mean Score on the Protocol Biopsies in the Two Treatment Groups Tubular atrophy	0.6 score on a scale Standard Deviation 0.56	0.88 score on a scale Standard Deviation 0.8
Mean Score on the Protocol Biopsies in the Two Treatment Groups Graft glomerulopathy	0.14 score on a scale Standard Deviation 0.45	0 score on a scale Standard Deviation 0
Mean Score on the Protocol Biopsies in the Two Treatment Groups Chronic vascular lesions	0.58 score on a scale Standard Deviation 0.9	0.64 score on a scale Standard Deviation 0.7
Mean Score on the Protocol Biopsies in the Two Treatment Groups Arteriolar hyalinosis	0.53 score on a scale Standard Deviation 0.7	0.69 score on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: 24 months

Patients with acute rejection lesions (including subclinical rejection) at 24 months according to Banff classification

Outcome measures

Measure	Steroids, Tacrolimus and Mycophenolate n=28 Participants Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=26 Participants Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Number of Participants With Acute Rejection Lesions	2 Participants	3 Participants

SECONDARY outcome

Timeframe: 24 months

Incidence of diabetes mellitus after kidney transplant in both groups at 1, 2, 3, 4, 6, 9, 12, 18 and 24 months

Outcome measures

Measure	Steroids, Tacrolimus and Mycophenolate n=39 Participants Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=36 Participants Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Incidence of Diabetes Mellitus	10 Participants	6 Participants

SECONDARY outcome

Timeframe: 24 months

Lipid profile after kidney transplant in both groups at 24 months

Outcome measures

Measure	Steroids, Tacrolimus and Mycophenolate n=39 Participants Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=36 Participants Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Lipid Profile HDL	51 mg/dl Standard Deviation 14	44.7 mg/dl Standard Deviation 10
Lipid Profile LDL	86 mg/dl Standard Deviation 21	92 mg/dl Standard Deviation 18
Lipid Profile Triglycerides	140 mg/dl Standard Deviation 54	127 mg/dl Standard Deviation 7.8
Lipid Profile Cholesterol	164 mg/dl Standard Deviation 28	161 mg/dl Standard Deviation 27

SECONDARY outcome

Timeframe: 24 months

Blood pressure after kidney transplant in both groups at 24 months

Outcome measures

Measure	Steroids, Tacrolimus and Mycophenolate n=39 Participants Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=36 Participants Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Blood Pressure Systolic BP	133 mmHg Standard Deviation 16	125 mmHg Standard Deviation 15
Blood Pressure Diastolic BP	74.9 mmHg Standard Deviation 11	76 mmHg Standard Deviation 9.7

SECONDARY outcome

Timeframe: 24 months

Renal function after kidney transplant in both groups at 24 months measured according to the creatinine (mg/dL) concentrations

Outcome measures

Measure	Steroids, Tacrolimus and Mycophenolate n=39 Participants Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=36 Participants Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Renal Function	1.34 mg/dl Standard Deviation 0.4	1.4 mg/dl Standard Deviation 0.4

SECONDARY outcome

Timeframe: At 24 months

The Basle scale was used to assess adherence (BAASIS questionnaire) to immunosuppressive therapy.

Outcome measures

Measure	Steroids, Tacrolimus and Mycophenolate n=39 Participants Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=36 Participants Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups Forgot at least one dose during last 4 weeks	0 Participants	1 Participants
Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups Dose taken 2 hours or more before or after time	3 Participants	11 Participants

SECONDARY outcome

Timeframe: 24 months

Patient survival after kidney transplant in both groups

Outcome measures

Measure	Steroids, Tacrolimus and Mycophenolate n=39 Participants Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=36 Participants Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Patient Survival	39 Participants	36 Participants

SECONDARY outcome

Timeframe: 24 months

Graft survival after kidney transplant in both groups

Outcome measures

Measure	Steroids, Tacrolimus and Mycophenolate n=39 Participants Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=36 Participants Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Graft Survival	39 Participants	36 Participants

SECONDARY outcome

Timeframe: 24 months

Renal function after kidney transplant in both groups at 24 months measured according to the proteinuria (mg/24 h) concentrations

Outcome measures

Measure	Steroids, Tacrolimus and Mycophenolate n=39 Participants Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=36 Participants Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Renal Function	209 mg/24h Standard Deviation 185	148 mg/24h Standard Deviation 82

Adverse Events

Steroids, Tacrolimus and Mycophenolate

Serious events: 10 serious events

Other events: 0 other events

Deaths: 0 deaths

Tacrolimus and Mycophenolate

Serious events: 15 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Steroids, Tacrolimus and Mycophenolate n=52 participants at risk Normal treatment arm Prednisone continuation: Continuation of steroids	Tacrolimus and Mycophenolate n=53 participants at risk Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Prednisone withdrawal: Withdrawal of steroids
Renal and urinary disorders Infection	9.6% 5/52 • 24 months	22.6% 12/53 • 24 months
Cardiac disorders Cardiovascular Disease	5.8% 3/52 • 24 months	3.8% 2/53 • 24 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	3.8% 2/52 • 24 months	1.9% 1/53 • 24 months

Other adverse events

Adverse event data not reported

Additional Information

Dr. Domingo Hernandez

Hospital Regional Universitario de Málaga

Phone: 951291174

Email: domingohernandez@gmail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place