Therapeutic Evaluation of Steroids in IgA Nephropathy Global Study (TESTING Low Dose Study)
NCT ID: NCT01560052
Last Updated: 2021-09-23
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
503 participants
INTERVENTIONAL
2012-05-05
2021-07-23
Brief Summary
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Detailed Description
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The TESTING study was established to compare the effects of oral methylprednisolone 0.8 mg/kg/day weaning over 6-8 months, to matching placebo on the risk of kidney failure events, using a double-blind, randomised, controlled design.
After the randomisation of 262 participants to the TESTING an imbalance in serious adverse events was noted between the methylprednisolone and placebo arms of the trial by the Data Monitoring Committee, mostly due to infection. As the data also suggested likely benefit on kidney outcomes, a further 240 participants will be randomised to methylprednisolone 0.4 mg/kg/day compared to matching placebo (The TESTING low-dose group). Oral sulfamethoxazole/trimethoprim will also be provided to reduce the risk of infection All participants will undergo long term follow-up until at least 160 primary outcome events are observed (expected to be an average of at least 4 years), and the effects of steroids on the risk of the composite kidney outcome will be assessed on the study population as a whole, stratified for treatment regimen so long as there is no evidence of significant heterogeneity in the efficacy at reducing the primary outcome.
Each of the original and the low-dose cohorts in TESTING will also have separate power to detect reductions in proteinuria and effects on average eGFR, along with effects on important safety outcomes with the steroid regimens used.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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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.
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.
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
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
Interventions
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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.
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
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
Exclusion Criteria
* 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.
18 Years
ALL
No
Sponsors
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Peking University First Hospital
OTHER
The George Institute
OTHER
Responsible Party
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Principal Investigators
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Hong Zhang
Role: PRINCIPAL_INVESTIGATOR
Peking University
Vlado Perkovic
Role: PRINCIPAL_INVESTIGATOR
The George Institute
Locations
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Concord Repatriation and General Hospital
Concord, New South Wales, Australia
Nepean Hospital
Kingswood, New South Wales, Australia
Royal North Shore Hospital
St Leonards, New South Wales, Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Royal Melbourne Hospital
Melbourne, Victoria, Australia
University of Calgary/Alberta Health Services
Calgary, Alberta, Canada
University of Alberta Hospitals
Edmonton, Alberta, Canada
St Pauls Hospital
Vancouver, British Columbia, Canada
St. Joseph's Healthcare
Hamiliton, Ontario, Canada
London Health Sciences Centre
London, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Toronto General Hospital,
Toronto, Ontario, Canada
Hôpital Maisonneuve-Rosemont
Montreal, Quebec, Canada
Chinese PLA General Hospital (301 Hospital)
Beijing, Beijing Municipality, China
The First Affiliated Hospital, Sun Yat-Sen University
Guangzhou, Guangdong, China
Guangdong Provincial People's Hospital, Guangzhou
Guangzhou, Guangdong, China
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China
The Second Hospital of Hebei Medical University
Shijiazhuang, Hebei, China
The Third Hospital of Hebei Medical University
Shijiazhuang, Hebei, China
The First Affiliated Hospital of Henan University of Science &Technology
Luoyang, Henan, China
Henan Provincial People's Hospital
Zhengzhou, Henan, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
ongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
Wuhan, Hubei, China
Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
Renmin Hospital, Wuhan University
Wuhan, Hubei, China
The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology,
Baotou, Inner Mongolia, China
Inner Mongolia People's Hospital
Hohhot, Inner Mongolia, China
General Hospital of Eastern Theater Command
Nanjing, Jiangsu, China
The First Affiliated Hospital with Nanjing Medical University
Nanjing, Jiangsu, China
Jilin Province FAW General Hospital [Jilin University Fourth Hospital]
Changchun, Jilin, China
he First Affiliated Hospital of Dalian Medical University, Dalian
Dalian, Liaoning, China
Shengjing Hospital Of China Medical University
Shengyang, Liaoning, China
Qilu Hospital of Shandong University
Jinan, Shandong, China
The First Affiliated Hospital of Shangdong First Medical University,Shangdong Provincial Qianfoshin
Jinan, Shandong, China
Shandong Provincial Hospital
Jinan, Shandong, China
Jinan Military General Hospital
Jinan, Shandong, China
Yantai Yuhuangding Hospital
Yantai, Shandong, China
he Second Hospital of Shanxi Medical University, Taiyuan
Taiyuan, Shanxi, China
West China Hospital of Sichuan University
Chengdu, Sichuan, China
Sichuan Academy of Medical Science, Sichuan Provincial People's Hospital
Chengdu, Sichuan, China
The First Affiliated Hospital, Zhejiang University of Medicine
Hangzhou, Zhejiang, 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, , China
Peking University First Hospital
Beijing, , China
Peking University People's Hospital
Beijing, , China
Beijing Hospital
Beijing, , China
Peking University Third Hospital
Beijing, , China
XinQiao Hospital, Third Military Medical University
Chongqing, , China
Renji Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, , China
Ruijin Hospital, Shanghai Jiaotong University, School of Medicine
Shanghai, , China
Huashan Hospital, Medical Centre of Fudan University
Shanghai, , China
Princess Margaret Hospital
Kowloon, , Hong Kong
Osmania General Hospital
Hyderabad, Andhra Pradesh, India
Nizam's Institute of Medical Science
Hyderabad, Andhra Pradesh, India
Calicut Medical College
Kozhikode, Kerala, India
Post Graduate Institue of Medical Education and Reasearch
Chandigarh, Punjab, India
Madras Medical College
Chen, Tamil Nadu, India
Sanjay Gandhi Post Graduate Institute of Medical Science
Lucknow, Uttar Pradesh, India
Hospital Sultanah Aminah
Johor Bahru, Johor, Malaysia
Hospital Kuala Lumpur
Kuala Lumpur, Kulala Lumpur, Malaysia
Hospital Tuanku Jaafar Seremban
Seremban, Negri Seremban, Malaysia
Hospital Raja Permaisuri Bainun
Ipoh, Perak, Malaysia
Hospital Umum Sarawak
Kuching, Samarahan, Malaysia
University Malaysia Medical Centre
Kuala Lumpur, , Malaysia
Countries
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References
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Lv 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.
Lv 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.
Yeo SC, Liew A, Barratt J. Emerging therapies in immunoglobulin A nephropathy. Nephrology (Carlton). 2015 Nov;20(11):788-800. doi: 10.1111/nep.12527.
Other Identifiers
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GI-R-01-2011
Identifier Type: -
Identifier Source: org_study_id
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