Therapeutic Evaluation of Steroids in IgA Nephropathy Global Study (TESTING Low Dose Study) (TESTING)
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| ClinicalTrials.gov Identifier: NCT01560052 |
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Recruitment Status :
Completed
First Posted : March 21, 2012
Last Update Posted : September 23, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| IgA Glomerulonephritis | Drug: methylprednisolone Drug: Placebo | Not Applicable |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 503 participants |
| 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 |
| Actual Study Start Date : | May 5, 2012 |
| Actual Primary Completion Date : | July 23, 2021 |
| Actual Study Completion Date : | July 23, 2021 |
| Arm | Intervention/treatment |
|---|---|
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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 |
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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 |
- 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
- 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 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
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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.
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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.
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
Show 66 study locations
| Principal Investigator: | Hong Zhang | Peking University | |
| Principal Investigator: | Vlado Perkovic | The George Institute |
| Responsible Party: | The George Institute |
| ClinicalTrials.gov Identifier: | NCT01560052 |
| Other Study ID Numbers: |
GI-R-01-2011 |
| First Posted: | March 21, 2012 Key Record Dates |
| Last Update Posted: | September 23, 2021 |
| Last Verified: | September 2021 |
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end stage kidney disease IgA nephropathy |
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Kidney Diseases Glomerulonephritis, IGA Glomerulonephritis Urologic Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Male Urogenital Diseases Nephritis Autoimmune Diseases Immune System Diseases Methylprednisolone Methylprednisolone Acetate Methylprednisolone Hemisuccinate Prednisolone |
Prednisolone acetate Prednisolone hemisuccinate Prednisolone phosphate 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 |