INFORMATION FOR PHYSICIANS

• Inclusion and Exclusion Criteria
• Study Protocol [.pdf]
• Manual of Operations
• Recruitment and Retention Documents and Forms
• Site Registration Form [.pdf]
• Human Subject Protection Training
• Become a Participating Site [e-mail]
• FSGS Database and Web-Resource Refresher Training [.ppt]

Inclusion and Exclusion Criteria

Inclusion

1. Age 2-40 years at onset of FSGS

2. Age < 40 years at time of randomization (randomization date before 41st birthday)

3. Estimated GFR > 40 ml/min/1.73 m² at most recent measure prior to randomization¹

a) For patients < age 18 years: Schwartz formula
b) For patients > age 18 years: Cockroft-Gault formula

4. Up/c > 1.0 g/g creatinine on first am void at time of randomization¹

5. Biopsy confirmed as primary FSGS (including all subtypes) by study pathologist. A minimum of 1 glomerulus demonstrating segmental sclerosis on light microscopy will be required to confirm the diagnosis.

6. Steroid resistance: The participant must have demonstrated steroid resistance (defined as a failure to achieve a sustained Up/c ≤ 1.0) based on at least one treatment course with high dose steroids prior to randomization which satisfies both of the following conditions:

1. minimal treatment duration of at least 4 weeks
2. minimum cumulative dose of 56 mg/kg or 1,680 mg of prednisone or its equivalent.

In addition, the patient must not have had a complete remission of proteinuria (Up/c < 0.2 or dipstick urine protein 0/trace) subsequent to the latest qualifying 8-week course demonstrating steroid resistance.

7. Willingness to follow the clinical trial protocol, including medications, and baseline and follow-up visits and procedures.

Patients may be taking ACEi, ARB, Vitamin E, or lipid-lowering therapy.

[back to top]

Exclusion Criteria

1. Secondary FSGS 2. Prior therapy with sirolimus, CSA, tacrolimus, MMF, or azathioprin (Imuran)

3. Treated with cytoxan, chlorambucil, levamisole, methotrexate, or nitrogen mustard in the last 30 days

4. Lactation, pregnancy, or refusal of birth control in women of child-bearing potential¹

5. Participation in another therapeutic trial concurrently or 30 days prior to randomization¹

6. Active/serious infection (including, but not limited to Hepatitis B or C, HIV)¹

7. Malignancy

8. Blood pressure > 140/95 or > 95th percentile for age/height.¹

9. Patient is receiving 4 or more antihypertensive agents for the primary purpose of controlling blood pressure.¹

10. Patients with previously diagnosed diabetes mellitus Type I or II: the diagnosis of DM I or II will be based on local criteria for patients with an established diagnosis. If hyperglycemia is detected during the screening period, the WHO criteria for the diagnosis of DM I and II will be used.

11. Clinical evidence of cirrhosis or chronic active liver disease

12. Abnormal laboratory values at the time of study entry:

1. Absolute neutrophil count (ANC) < 2000/mm³, or
2. Hematocrit (HCT) < 28%

13. History of significant gastrointestinal disorder, e.g, severe chronic diarrhea (> 5 watery stools per day) or active peptic ulcer disease.

14. Organ transplantation

15. Obesity (based on estimated dry weight at onset of disease prior to steroid therapy) defined as

1. BMI > 97th percentile for age if age 2-20 years
2. BMI > 40 kg/m 2 for age =21 years

16. Allergy to study medications

17. Inability to consent/assent

[back to top]

¹ Patients with conditions meeting exclusion criteria at a particular evaluation for eligibility may be re-evaluated at a later time to determine if the conditions have changed so that all entry criteria are met. In particular, if blood pressure > 140/95 or > 95th percentile for age/height while the patient is on less than three antihypertensive agents, the patient may be re-evaluated for eligibility after adding other antihypertensive agents so long as the total number of agents does not exceed three. Click here for current information.