Therapeutic Evaluation of Steroids in IgA Nephropathy Global Study (TESTING Low Dose Study)
TESTING
1 other identifier
interventional
503
6 countries
66
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started May 2012
Longer than P75 for not_applicable
66 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 15, 2012
CompletedFirst Posted
Study publicly available on registry
March 21, 2012
CompletedStudy Start
First participant enrolled
May 5, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 23, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
July 23, 2021
CompletedSeptember 23, 2021
September 1, 2021
9.2 years
March 15, 2012
September 21, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progressive kidney failure
Progressive kidney failure, which is a composite of a 40% decrease in eGFR, the development of end stage kidney disease defined as a need for maintenance dialysis or kidney transplantation, and death due to kidney disease.
1-6 years
primary outcome for low dose cohort
Change in proteinuria from baseline at 6 and 12 months Mean change in eGFR at 6 and 12 months
1 year
Secondary Outcomes (6)
The composite of ESKD, 30% decrease in eGFR and all cause death
1-6 years
The composite of ESKD 40% decrease in eGFR and all cause death
1-6 years
The composite of ESKD 50% decrease in eGFR and all cause death
1-6 years
Annual eGFR decline rate
1-6 years
Each ESKD , death due to kidney disease and all cause death
1-6 years
- +1 more secondary outcomes
Study Arms (2)
oral methylprednisolone
ACTIVE COMPARATORoral 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
PLACEBO COMPARATOROriginal 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
Interventions
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.
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
Eligibility Criteria
You may qualify if:
- IgA nephropathy proven on renal biopsy.
- 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.
- eGFR: 30 to 120ml/min per 1.73m²(inclusive) while receiving maximum tolerated RAS blockade
You may not qualify if:
- 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.
- 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.
- Systemic immunosuppressive therapy in the previous year.
- Malignant /uncontrolled hypertension (\>160mm systolic or 110mmHg diastolic)
- Current unstable kidney function for other reasons, e.g. macrohaematuria induced acute kidney injury
- Age \<18 years old
- Secondary IgA nephropathy: e.g. due to lupus, liver cirrhosis, Henoch- Schonlein purpura
- Patients who are unlikely to comply with the study protocol in the view of the treating physician.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- The George Institutelead
- Peking University First Hospitalcollaborator
Study Sites (66)
Concord Repatriation and General Hospital
Concord, New South Wales, 2139, Australia
Nepean Hospital
Kingswood, New South Wales, 2747, Australia
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
Royal Melbourne Hospital
Melbourne, Victoria, 3052, Australia
University of Calgary/Alberta Health Services
Calgary, Alberta, T2R 0X7, Canada
University of Alberta Hospitals
Edmonton, Alberta, T6G 2B7, Canada
St Pauls Hospital
Vancouver, British Columbia, V6Z 1Y6, Canada
St. Joseph's Healthcare
Hamiliton, Ontario, L8N 4A6, Canada
London Health Sciences Centre
London, Ontario, N6A 5A5, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
Toronto General Hospital,
Toronto, Ontario, M5G 2N2, Canada
Hôpital Maisonneuve-Rosemont
Montreal, Quebec, H1T 2M4, Canada
Chinese PLA General Hospital (301 Hospital)
Beijing, Beijing Municipality, China
The First Affiliated Hospital, Sun Yat-Sen University
Guangzhou, Guangdong, 510080, China
Guangdong Provincial People's Hospital, Guangzhou
Guangzhou, Guangdong, China
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036, China
The Second Hospital of Hebei Medical University
Shijiazhuang, Hebei, 050005, China
The Third Hospital of Hebei Medical University
Shijiazhuang, Hebei, 050051, China
The First Affiliated Hospital of Henan University of Science &Technology
Luoyang, Henan, 471003, China
Henan Provincial People's Hospital
Zhengzhou, Henan, 450003, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052, China
ongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
Wuhan, Hubei, 430022, China
Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430022, China
Renmin Hospital, Wuhan University
Wuhan, Hubei, 430060, China
The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology,
Baotou, Inner Mongolia, 014010, China
Inner Mongolia People's Hospital
Hohhot, Inner Mongolia, 010017, China
General Hospital of Eastern Theater Command
Nanjing, Jiangsu, 210002, China
The First Affiliated Hospital with Nanjing Medical University
Nanjing, Jiangsu, 210029, China
Jilin Province FAW General Hospital [Jilin University Fourth Hospital]
Changchun, Jilin, 130011, China
he First Affiliated Hospital of Dalian Medical University, Dalian
Dalian, Liaoning, 116011, China
Shengjing Hospital Of China Medical University
Shengyang, Liaoning, China
Qilu Hospital of Shandong University
Jinan, Shandong, 250012, China
The First Affiliated Hospital of Shangdong First Medical University,Shangdong Provincial Qianfoshin
Jinan, Shandong, 250014, China
Shandong Provincial Hospital
Jinan, Shandong, 250021, China
Jinan Military General Hospital
Jinan, Shandong, China
Yantai Yuhuangding Hospital
Yantai, Shandong, 264000, China
he Second Hospital of Shanxi Medical University, Taiyuan
Taiyuan, Shanxi, 030001, China
West China Hospital of Sichuan University
Chengdu, Sichuan, 610041, China
Sichuan Academy of Medical Science, Sichuan Provincial People's Hospital
Chengdu, Sichuan, 610072, China
The First Affiliated Hospital, Zhejiang University of Medicine
Hangzhou, Zhejiang, 310003, China
Hangzhou Hospital of Traditional Chinese Medicine,
Hangzhou, Zhejiang, China
Ningbo Urology & Nephrology Hospital
Ningbo, Zhejiang, China
Zhejiang Provincial People's Hospital
Sangzhou, Zhejiang, China
Beijing Anzhen Hospital, Capital Medical University
Beijing, 100029, China
Peking University First Hospital
Beijing, 100034, China
Peking University People's Hospital
Beijing, 100035, China
Beijing Hospital
Beijing, 100730, China
Peking University Third Hospital
Beijing, China
XinQiao Hospital, Third Military Medical University
Chongqing, 400037, China
Renji Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, 200001, China
Ruijin Hospital, Shanghai Jiaotong University, School of Medicine
Shanghai, 200025, China
Huashan Hospital, Medical Centre of Fudan University
Shanghai, 200040, China
Princess Margaret Hospital
Kowloon, Hong Kong
Osmania General Hospital
Hyderabad, Andhra Pradesh, 500012, India
Nizam's Institute of Medical Science
Hyderabad, Andhra Pradesh, 500082,, India
Calicut Medical College
Kozhikode, Kerala, 673008,, India
Post Graduate Institue of Medical Education and Reasearch
Chandigarh, Punjab, 160 012, India
Madras Medical College
Chen, Tamil Nadu, 600037, India
Sanjay Gandhi Post Graduate Institute of Medical Science
Lucknow, Uttar Pradesh, 226014, India
Hospital Sultanah Aminah
Johor Bahru, Johor, 80100, Malaysia
Hospital Kuala Lumpur
Kuala Lumpur, Kulala Lumpur, 50586, Malaysia
Hospital Tuanku Jaafar Seremban
Seremban, Negri Seremban, 70300, Malaysia
Hospital Raja Permaisuri Bainun
Ipoh, Perak, 30990, Malaysia
Hospital Umum Sarawak
Kuching, Samarahan, 93586, Malaysia
University Malaysia Medical Centre
Kuala Lumpur, 59100, Malaysia
Related Publications (4)
Xu LL, Zhou XJ, Bi W, Zhang P, Shi SF, Liu LJ, Lv JC, Zhang H. Genetic Determinants of Steroid Responsiveness in IgA Nephropathy. J Am Soc Nephrol. 2025 Dec 11. doi: 10.1681/ASN.0000000977. Online ahead of print. No abstract available.
PMID: 41563292DERIVEDLv J, Wong MG, Hladunewich MA, Jha V, Hooi LS, Monaghan H, Zhao M, Barbour S, Jardine MJ, Reich HN, Cattran D, Glassock R, Levin A, Wheeler DC, Woodward M, Billot L, Stepien S, Rogers K, Chan TM, Liu ZH, Johnson DW, Cass A, Feehally J, Floege J, Remuzzi G, Wu Y, Agarwal R, Zhang H, Perkovic V; TESTING Study Group. Effect of Oral Methylprednisolone on Decline in Kidney Function or Kidney Failure in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2022 May 17;327(19):1888-1898. doi: 10.1001/jama.2022.5368.
PMID: 35579642DERIVEDLv J, Zhang H, Wong MG, Jardine MJ, Hladunewich M, Jha V, Monaghan H, Zhao M, Barbour S, Reich H, Cattran D, Glassock R, Levin A, Wheeler D, Woodward M, Billot L, Chan TM, Liu ZH, Johnson DW, Cass A, Feehally J, Floege J, Remuzzi G, Wu Y, Agarwal R, Wang HY, Perkovic V; TESTING Study Group. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017 Aug 1;318(5):432-442. doi: 10.1001/jama.2017.9362.
PMID: 28763548DERIVEDYeo SC, Liew A, Barratt J. Emerging therapies in immunoglobulin A nephropathy. Nephrology (Carlton). 2015 Nov;20(11):788-800. doi: 10.1111/nep.12527.
PMID: 26032537DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Hong Zhang
Peking University
- PRINCIPAL INVESTIGATOR
Vlado Perkovic
The George Institute
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 15, 2012
First Posted
March 21, 2012
Study Start
May 5, 2012
Primary Completion
July 23, 2021
Study Completion
July 23, 2021
Last Updated
September 23, 2021
Record last verified: 2021-09