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Therapeutic Evaluation of Steroids in IgA Nephropathy Global Study (TESTING Low Dose Study) (TESTING)

This study is currently recruiting participants.
Verified February 2017 by The George Institute
Sponsor:
ClinicalTrials.gov Identifier:
NCT01560052
First Posted: March 21, 2012
Last Update Posted: February 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Peking University First Hospital
Information provided by (Responsible Party):
The George Institute
  Purpose
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.

Condition Intervention
IgA Glomerulonephritis Drug: methylprednisolone Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Therapeutic Evaluation of Steroids in IgA Nephropathy Global Study Low Dose Study

Resource links provided by NLM:


Further study details as provided by The George Institute:

Primary Outcome Measures:
  • Progressive kidney failure [ Time Frame: 1-6 years ]
    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.

  • primary outcome for low dose cohort [ Time Frame: 1 year ]
    Change in proteinuria from baseline at 6 and 12 months Mean change in eGFR at 6 and 12 months


Secondary Outcome Measures:
  • The composite of ESKD, 30% decrease in eGFR and all cause death [ Time Frame: 1-6 years ]
  • The composite of ESKD 40% decrease in eGFR and all cause death [ Time Frame: 1-6 years ]
  • The composite of ESKD 50% decrease in eGFR and all cause death [ Time Frame: 1-6 years ]
  • Annual eGFR decline rate [ Time Frame: 1-6 years ]
  • Each ESKD , death due to kidney disease and all cause death [ Time Frame: 1-6 years ]
  • Time averaged proteinuria post-randomisation [ Time Frame: 1-6 years ]

Estimated Enrollment: 500
Study Start Date: April 2012
Estimated Study Completion Date: June 2023
Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: 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.

Other Name: Medrol
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

Drug: 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


Detailed Description:

IgA glomerulonephritis is the most common primary glomerulonephritis, and immunosuppression with steroids has been suggested to be a potential protective therapy, although the benefits and risks have not been clearly established.

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01560052


Contacts
Contact: Vlado Perkovic +61299934500 vperkovic@george.org.au

  Hide Study Locations
Locations
Australia, New South Wales
Concord Repatriation and General Hospital Recruiting
Concord, New South Wales, Australia, 2139
Principal Investigator: Mona Razivian         
Royal North Shore Hospital Recruiting
St Leonards, New South Wales, Australia, 2065
Principal Investigator: Bruce Cooper, Dr         
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Principal Investigator: Chen Auh Peh         
Australia, Victoria
Royal Melbourne Hospital Recruiting
Melbourne, Victoria, Australia, 3052
Contact    61 3 9342 7119      
Principal Investigator: A/Professor K Nicholls         
Canada, Alberta
University of Calgary/Alberta Health Services Not yet recruiting
Calgary, Alberta, Canada, T2R 0X7
Principal Investigator: Louis Girard         
University of Alberta Hospitals Not yet recruiting
Edmonton, Alberta, Canada, T6G 2B7
Principal Investigator: Neesh Pannu         
Canada, British Columbia
St Pauls Hospital Not yet recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
Principal Investigator: Sean Barbour         
Canada, Ontario
St. Joseph's Healthcare Not yet recruiting
Hamiliton, Ontario, Canada, L8N 4A6
Principal Investigator: Christian Rabbat         
London Health Sciences Centre Not yet recruiting
London, Ontario, Canada, N6A 5A5
Principal Investigator: Susan Huang         
Sunnybrook Health Sciences Centre Not yet recruiting
Toronto, Ontario, Canada, M4N 3M5
Principal Investigator: Michelle Hladunewich         
Toronto General Hospital, Not yet recruiting
Toronto, Ontario, Canada, M5G 2N2
Principal Investigator: Daniel Cattran         
Canada, Quebec
Hôpital Maisonneuve-Rosemont Not yet recruiting
Montreal, Quebec, Canada, H1T 2M4
Principal Investigator: Louis Phillipe Laurin         
China, Beijing
Chinese PLA General Hospital Recruiting
Beijing, Beijing, China
Principal Investigator: Guangyan Cai         
China, Guangdong
First Affiliated Hospital, Sun Yat-Sen University Recruiting
Guangzhou, Guangdong, China, 510080
Principal Investigator: Xueqing Yu         
Guangdong Province People's Hosptial Recruiting
Guangzhou, Guangdong, China
Principal Investigator: Wei Shi         
Peking University Shenzhen Hospital Recruiting
Shenzhen, Guangdong, China, 518036
Principal Investigator: Qiong Luo         
China, Hebei
The Second Hospital of Hebei Medical University Recruiting
Shijiazhuang, Hebei, China, 050005
Principal Investigator: Shuxia Fu         
The Third Hospital of Hebei Medical University Recruiting
Shijiazhuang, Hebei, China, 050051
Principal Investigator: Ying Li         
China, Henan
First Affiliated Hospital of Henan University of Science &Technology Recruiting
Luoyang, Henan, China, 471003
Principal Investigator: Zhiling Guo         
Henan Provincial People's Hospital Recruiting
Zhengzhou, Henan, China, 450003
Principal Investigator: Bing Liu         
The First Affiliated Hospital of Zhengzhou University Recruiting
Zhengzhou, Henan, China, 450052
Principal Investigator: Zhangsuo Liu         
China, Hubei
Tongji Hospital of Huazhong University of Science and Technology Recruiting
Wuhan, Hubei, China, 430022
Principal Investigator: Gang Xu         
Union Hospital,Tongji Medical College,Huazhong University of Science and Technology Recruiting
Wuhan, Hubei, China, 430022
Principal Investigator: Jianshe Liu         
Renmin Hospital, Wuhan University Recruiting
Wuhan, Hubei, China, 430060
Principal Investigator: Guohua Ding         
China, Inner Mongolia
First Affiliated Hospital of Inner Mongolia, Baotou Medical College Recruiting
Baotou, Inner Mongolia, China, 014010
Principal Investigator: Caili Wang         
Inner Mongolia People's Hospital Recruiting
Hohhot, Inner Mongolia, China, 010017
Principal Investigator: Li Gong         
China, Jiangsu
Nanjing General Hospital of Nanjing Military Command Recruiting
Nanjing, Jiangsu, China, 210002
Principal Investigator: Haitao Zhang         
Zhong Da Hospital, Southeast University Withdrawn
Nanjing, Jiangsu, China, 210009
First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) Withdrawn
Nanjing, Jiangsu, China, 210029
China, Jilin
Fourth Hospital Affiliated to Jilin University (FAW General Hospital) Recruiting
Changchun, Jilin, China, 130011
Principal Investigator: Xiaoxuan Zhang         
Fourth Hospital, affiliated to Jili University FAW Gen eral Hospital Recruiting
Changchun, Jilin, China
Contact: Zhang Xiaoxuan         
Principal Investigator: Zhang Xiaoxuan, Dr         
China, Liaoning
First Affiliated Hospital of Dalian Medical University Recruiting
Dalian, Liaoning, China, 116011
Principal Investigator: Hongli Lin         
Shengjing Hospital Of China Medical University Recruiting
Shengyang, Liaoning, China
Principal Investigator: Detian Li         
China, Shandong
Qilu Hospital of Shandong University Recruiting
Jinan, Shandong, China, 250012
Principal Investigator: Zhao Hu         
Qianfoshan Hospital Affiliated to Shandong University Recruiting
Jinan, Shandong, China, 250014
Principal Investigator: Dongmei Xu         
Provincial Hospital Affliated to Shandong University Recruiting
Jinan, Shandong, China, 250021
Principal Investigator: Rong Wang         
Jinan Military General Hospital Recruiting
Jinan, Shandong, China
Principal Investigator: Aiping Zhang         
Yantai Yuhuangding Hospital Recruiting
Yantai, Shandong, China, 264000
Principal Investigator: Peng Li         
China, Shanxi
The Second Affiliated Hospital of Shanxi Medical University Recruiting
Taiyuan, Shanxi, China, 030001
Principal Investigator: Rongshan Li         
China, Sichuan
West China Hospital of Sichuan University Recruiting
Chengdu, Sichuan, China, 610041
Principal Investigator: Ping Fu         
Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital Recruiting
Chengdu, Sichuan, China, 610072
Principal Investigator: Guisen Li         
China, Zhejiang
The First Affiliated Hospital of Zhejiang University of Medicine Recruiting
Hangzhou, Zhejiang, China, 310003
Principal Investigator: Jianghua Chen         
Hangzhou Chinese Medicine Hospital Recruiting
Hangzhou, Zhejiang, China
Principal Investigator: Hongyu Chen         
Ningbo Urinary Kidney Disease Hospital Recruiting
Ningbo, Zhejiang, China
Principal Investigator: Beiyan Bao         
Zhejiang Provincal Peoples Hospital Recruiting
Sangzhou, Zhejiang, China
Principal Investigator: Qiang He         
China
Beijing Anzhen Hospital affiliated to Beijing Capital Medical University Recruiting
Beijing, China, 100029
Principal Investigator: Yipu Chen         
Peking University First Hospital Recruiting
Beijing, China, 100034
Principal Investigator: Jicheng Lv         
Principal Investigator: Hong Zhang         
Peking University People's Hospital Recruiting
Beijing, China, 100035
Principal Investigator: Mei Wang         
Beijing Hospital of the Ministry of Health Recruiting
Beijing, China, 100730
Principal Investigator: Hua Wu         
Beijing University Third Hospital Recruiting
Beijing, China
Principal Investigator: Yue Wang         
XinQiao Hospital, Third Military Medical University Recruiting
Chongqing, China, 400037
Principal Investigator: Jinghong Zhao         
Renji Hospital, Shanghai Jiaotong University School of Medicine Recruiting
Shanghai, China, 200001
Principal Investigator: Zhaohui Ni         
Ruijin Hospital, Shanghai Jiaotong University, School of Medicine Recruiting
Shanghai, China, 200025
Principal Investigator: Nan Chen         
Huashan Hospital Affiliated to Fudan University Recruiting
Shanghai, China, 200040
Principal Investigator: Fuming Lu         
The Chinese People's Liberation Army Shanghai 85th Hospital Withdrawn
Shanghai, China, 200052
Hong Kong
Princess Margaret Hospital Recruiting
Kowloon, Hong Kong
Principal Investigator: K S Fung         
India
Osmania General Hospital Not yet recruiting
Hyderabad, Andhra Pradesh, India, 500012
Principal Investigator: Manisha Sahay         
STAR Hospitals, Not yet recruiting
Hyderabad, Andhra Pradesh, India, 500034
Principal Investigator: Rajasekara Chakravarthi Madarasu         
Nizam's Institute of Medical Science Not yet recruiting
Hyderabad, Andhra Pradesh, India, 500082,
Principal Investigator: Sreebhushan Raju Raju         
Muljibhai Patel Urologcal Hospital Not yet recruiting
Nadiad, Gujarat, India, 387001
Principal Investigator: Sishir Gang         
Calicut Medical College Not yet recruiting
Kozhikode, Kerala, India, 673008,
Fortis Hospital Not yet recruiting
Delhi, New DelhiDelhi, India, 11070
Principal Investigator: Sanjeev Gulati         
Post Graduate Institue of Medical Education and Reasearch Not yet recruiting
Chandigarh, Punjab, India, 160 012
Principal Investigator: Raja Ramachandran         
Stanley Medical College Not yet recruiting
Chennai, Tamil Nadu, India, 600001
Principal Investigator: Edwin Fernando         
Madras Medical College Not yet recruiting
Chen, Tamil Nadu, India, 600037
Principal Investigator: Gopalakrishnan Natarajan         
Sanjay Gandhi Post Graduate Institute of Medical Science Not yet recruiting
Lucknow, Uttar Pradesh, India, 226014
Principal Investigator: Narayan Prasad         
Sponsors and Collaborators
The George Institute
Peking University First Hospital
Investigators
Principal Investigator: Hong Zhang Peking University
Principal Investigator: Vlado Perkovic The George Institute
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: The George Institute
ClinicalTrials.gov Identifier: NCT01560052     History of Changes
Other Study ID Numbers: GI-R-01-2011
First Submitted: March 15, 2012
First Posted: March 21, 2012
Last Update Posted: February 3, 2017
Last Verified: February 2017

Keywords provided by The George Institute:
end stage kidney disease
IgA nephropathy

Additional relevant MeSH terms:
Kidney Diseases
Glomerulonephritis, IGA
Glomerulonephritis
Urologic Diseases
Nephritis
Autoimmune Diseases
Immune System Diseases
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Trimethoprim
Sulfamethoxazole
Angiotensin-Converting Enzyme Inhibitors
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents