Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by The George Institute
Sponsor:
Collaborator:
Peking University First Hospital
Information provided by (Responsible Party):
The George Institute
ClinicalTrials.gov Identifier:
NCT01560052
First received: March 15, 2012
Last updated: February 1, 2017
Last verified: February 2017
  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: 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

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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01560052

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

  Show 66 Study Locations
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
Study First Received: March 15, 2012
Last Updated: February 1, 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

ClinicalTrials.gov processed this record on April 21, 2017