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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01560052




Registration number
NCT01560052
Ethics application status
Date submitted
15/03/2012
Date registered
21/03/2012
Date last updated
23/09/2021

Titles & IDs
Public title
Therapeutic Evaluation of Steroids in IgA Nephropathy Global Study (TESTING Low Dose Study)
Scientific title
Therapeutic Evaluation of Steroids in IgA Nephropathy Global Study Low Dose Study
Secondary ID [1] 0 0
GI-R-01-2011
Universal Trial Number (UTN)
Trial acronym
TESTING
Linked study record

Health condition
Health condition(s) or problem(s) studied:
IgA Glomerulonephritis 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - methylprednisolone
Treatment: Drugs - Placebo

Active Comparator: oral methylprednisolone - oral methylprednisolone
Original Cohort:
Methylprednisolone group; start at 0.8mg/kg/day with a maximal 48mg/kg/day x 2months, taper by 8mg/day every month with optimal blood pressure control and full dose of ACE inhibitors or ARBs as recommended by guidelines.
Low Dose Cohort:
Methylprednisolone group; start at 0.4mg /kg/day with a maximal dose of 32mg/day and a minimum dose of 24mg/day, reducing over 6-9months.
All participants will also receive standard guideline based care, without steroid therapy. Prophylactic trimethoprim/sulfamethoxazole (a single strength tablet daily or half a double strength tablet daily) will be used during the first 3 months in the low-dose cohort, after randomisation, for the prevention of severe PJP infection, unless there is a documented sulfa allergy.

Placebo Comparator: placebo - Original Cohort:
Matching placebo; Optimal blood pressure control and full dose of ACE inhibitors or ARBs as recommended by guidelines; Low Dose Cohort; Matching placebo: Optimal blood pressure control and full dose of ACE inhibitors or ARBs as recommended by guidelines.
All participants will also receive standard guideline based care, without steroid therapy. Prophylactic trimethoprim/sulfamethoxazole (a single strength tablet daily or half a double strength tablet daily) will be used during the first 3 months in the low-dose cohort, after randomisation, for the prevention of severe PJP infection, unless there is a documented sulfa allergy


Treatment: Drugs: methylprednisolone
Original Cohort:
Oral methylprednisolone or placebo 0.8mg/kg/day with a maximum of 48mg/day x 2months, taper by 8mg/day every month, patients will also receive optimal blood pressure control and full dose of ACE inhibitors or ARBs as recommended by guidelines
Low Dose Cohort:
Oral methylprednisolone or placebo 0.4mg/kg/day with a maximum 32mg/day and minimum of 24mg/day then reducing over 6-9months. All the patients will also receive optimal blood pressure control and full dose of ACE inhibitors or ARBs as recommended by guidelines throughout the trial.
Prophylactic trimethoprim/sulfamethoxazole (a single strength tablet daily or half a double strength tablet daily) will be used during the first 3 months after randomisation in the low dose cohort, for the prevention of severe PJP infection, unless there is a documented sulfa allergy.

Treatment: Drugs: Placebo
Intervention: Drug: Placebo
Original Cohort:
Matching placebo tablets, all the patients will receive optimal blood pressure control and full dose of ACE inhibitors or ARBs as recommended by guidelines throughout the trial.
Low Dose cohort:
Matching placebo will be given reducing over 6-9months. All the patients will also receive optimal blood pressure control and full dose of ACE inhibitors or ARBs as recommended by guidelines throughout the trial.
Prophylactic trimethoprim/sulfamethoxazole (a single strength tablet daily or half a double strength tablet daily) will be used during the first 3 months after randomisation in the low dose cohort, for the prevention of severe PJP infection, unless there is a documented sulfa allergy
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progressive kidney failure
Timepoint [1] 0 0
1-6 years
Primary outcome [2] 0 0
primary outcome for low dose cohort
Timepoint [2] 0 0
1 year
Secondary outcome [1] 0 0
The composite of ESKD, 30% decrease in eGFR and all cause death
Timepoint [1] 0 0
1-6 years
Secondary outcome [2] 0 0
The composite of ESKD 40% decrease in eGFR and all cause death
Timepoint [2] 0 0
1-6 years
Secondary outcome [3] 0 0
The composite of ESKD 50% decrease in eGFR and all cause death
Timepoint [3] 0 0
1-6 years
Secondary outcome [4] 0 0
Annual eGFR decline rate
Timepoint [4] 0 0
1-6 years
Secondary outcome [5] 0 0
Each ESKD , death due to kidney disease and all cause death
Timepoint [5] 0 0
1-6 years
Secondary outcome [6] 0 0
Time averaged proteinuria post-randomisation
Timepoint [6] 0 0
1-6 years

Eligibility
Key inclusion criteria
1. IgA nephropathy proven on renal biopsy.

2. Proteinuria: >=1.0g/day while receiving maximum tolerated dose of RAS blockade
following the recommended treatment guidelines of each country where the trial is
conducted.

3. eGFR: 30 to 120ml/min per 1.73m²(inclusive) while receiving maximum tolerated RAS
blockade
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Indication for immunosuppressive therapy with corticosteroids, such as:

- Minimal change renal disease with IgA deposits Crescents present in >50% of
glomeruli on a renal biopsy within the last 12 months.

2. Contraindication to immunosuppressive therapy with corticosteroids, including:

- Active infection, including HBV infection or clinical evidence of latent or
active tuberculosis (nodules, cavities, tuberculoma, etc)

- Malignancy within the last 5 years, excluding treated non-melanoma skin cancers
(ie. squamous or basal cell carcinoma)

- Current or planned pregnancy or breastfeeding women of childbearing age who are
not able or willing to use adequate contraception.

3. Systemic immunosuppressive therapy in the previous year.

4. Malignant /uncontrolled hypertension (>160mm systolic or 110mmHg diastolic)

5. Current unstable kidney function for other reasons, e.g. macrohaematuria induced acute
kidney injury

6. Age <18 years old

7. Secondary IgA nephropathy: e.g. due to lupus, liver cirrhosis, Henoch- Schonlein
purpura

8. Patients who are unlikely to comply with the study protocol in the view of the
treating physician.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/05/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/07/2021
Sample size
Target
Accrual to date
Final
503
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Concord Repatriation and General Hospital - Concord
Recruitment hospital [2] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [3] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2747 - Kingswood
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3052 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
British Columbia
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
Canada
State/province [4] 0 0
Quebec
Country [5] 0 0
China
State/province [5] 0 0
Beijing
Country [6] 0 0
China
State/province [6] 0 0
Guangdong
Country [7] 0 0
China
State/province [7] 0 0
Hebei
Country [8] 0 0
China
State/province [8] 0 0
Henan
Country [9] 0 0
China
State/province [9] 0 0
Hubei
Country [10] 0 0
China
State/province [10] 0 0
Inner Mongolia
Country [11] 0 0
China
State/province [11] 0 0
Jiangsu
Country [12] 0 0
China
State/province [12] 0 0
Jilin
Country [13] 0 0
China
State/province [13] 0 0
Liaoning
Country [14] 0 0
China
State/province [14] 0 0
Shandong
Country [15] 0 0
China
State/province [15] 0 0
Shanxi
Country [16] 0 0
China
State/province [16] 0 0
Sichuan
Country [17] 0 0
China
State/province [17] 0 0
Zhejiang
Country [18] 0 0
China
State/province [18] 0 0
Chongqing
Country [19] 0 0
China
State/province [19] 0 0
Shanghai
Country [20] 0 0
Hong Kong
State/province [20] 0 0
Kowloon
Country [21] 0 0
India
State/province [21] 0 0
Andhra Pradesh
Country [22] 0 0
India
State/province [22] 0 0
Kerala
Country [23] 0 0
India
State/province [23] 0 0
Punjab
Country [24] 0 0
India
State/province [24] 0 0
Tamil Nadu
Country [25] 0 0
India
State/province [25] 0 0
Uttar Pradesh
Country [26] 0 0
Malaysia
State/province [26] 0 0
Johor
Country [27] 0 0
Malaysia
State/province [27] 0 0
Kulala Lumpur
Country [28] 0 0
Malaysia
State/province [28] 0 0
Negri Seremban
Country [29] 0 0
Malaysia
State/province [29] 0 0
Perak
Country [30] 0 0
Malaysia
State/province [30] 0 0
Samarahan
Country [31] 0 0
Malaysia
State/province [31] 0 0
Kuala Lumpur

Funding & Sponsors
Primary sponsor type
Other
Name
The George Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Peking University First Hospital
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the long-term efficacy and safety of low dose oral
methylprednisolone compared to matching placebo, on a background of routine RAS inhibitor
therapy, in preventing kidney events in patients with IgA nephropathy and features suggesting
a high risk of progression.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01560052
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Hong Zhang
Address 0 0
Peking University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01560052