Treatment of Renal Sarcoidosis by Methylprednisolone Bolus (CORTICOIDOSE)

Randomized, Multicentric Study Evaluating the Efficacy and the Safety of Methylprednisolone Bolus in the Treatment of Renal Sarcoidosis

Renal sarcoidosis treatment is based on steroids, but the dose and duration are unknown. Despite this treatment, most patients will have chronic kidney disease. From our previous studies, the investigators believe that high dose steroids by methylprednisolone bolus will improve patient outcome and renal function.

Study Overview

• Status: Terminated
• Conditions: Renal Sarcoidosis
• Intervention / Treatment: Drug: methylprednisolone bolus IV 15 mg/kg/d for 3 days.

Detailed Description

In a multicentric, randomized, open trial, the investigators will assess the efficacy of methylprednisolone bolus at 15mg/kg/d for 3 days before oral steroids on renal function improvement in renal sarcoidosis patients.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Service de Néphrologie et Dialyses, Hôpital Tenon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Acute kidney injury with estimated glomerular filtration rate (eGFR) < 60 mL/min/1,73 m2, defined by an increase of initial value > 25% or an increase of > 30 µmol/l, since at least 3 months.
• Sarcoidosis diagnostic criteria according to ATS/ERS/WASOG (Am J Respir Crit Care Med 1999)
• Renal biopsy compatible with renal sarcoidosis :
• Granulomatosis tubulo-interstitial nephropathy and extra-renal damage of histologically proved or suggestive sarcoidosis Or
• Tubulo-interstitial nephropathy without granuloma and extra-renal damage of histologically proved sarcoidosis
• Informed consent
• Patients with social security

Exclusion Criteria:

• Corticosteroids greater than 0,25 mg/kg/j prednisone equivalent
• Introduction of an immunosuppressant in the month before inclusion
• Another cause of renal granulomatosis or tubulo-interstitial nephropathy
• Isolated renal damage without extra-renal past or present damage for a sarcoidosis
• Chronic renal failure, prior sarcoidosis with eGFR < 30 mL/min/1,73 m2
• Acute renal failure from other causes. If hypercalcaemia is greater than 3 mmol/L, the correction of any dehydration will systematically salt intake, followed of renal function control before inclusion.
• Pregnancy, nursing
• Tuberculosis
• Uncontrolled sepsis
• Uncontrolled psychotic state
• Hypersensibility to methylprednisolone hemisuccinate
• Drugs prescription causing wave burst arrhythmia and/or long QT on ECG

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: oral prednisone; Oral prednisone 1 mg/kg/d for 30 days and progressive tapering of steroids, to get 0,5 mg/kg/d at M3 and 0,25 mg/kg/d at M6 and 5-10 mg at M12.
Experimental: methylprednisolone bolus; methylprednisolone bolus 15 mg/kg/d for 3 days before oral prednisone 1 mg/kg/d for 30 days and progressive tapering of steroids, to get 0,5 mg/kg/d at M3 and 0,25 mg/kg/d at M6 and 5-10 mg at M12.	Drug: methylprednisolone bolus IV 15 mg/kg/d for 3 days.; methylprednisolone bolus IV 15 mg/kg/d for 3 days.; Other Names: Methylprenisolone Mylan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients with a positive response defined by eGRF better than 100% compared to eGRF prior treatment or a normalization of renal function.	3 months after the beginning of the treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy (eGFR, percentage of patients with a eGRF < 60 ml/min/1.73m²)	1, 3, 6 and 12 months after the beginning of the treatment
Extra-renal manifestations	1, 3, 6 and 12 months after the beginning of the treatment
incidence of arrhythmias and cardiac conduction disease	1, 3, 6 and 12 months after the beginning of the treatment
fragility fracture	1, 3, 6 and 12 months after the beginning of the treatment
neuro-psychiatric troubles and infections	1, 3, 6 and 12 months after the beginning of the treatment
number of renal and extra-renal relapses.	1, 3, 6 and 12 months after the beginning of the treatment
Characterization of vitamin and calcium deficiencies by blood and urinary dosages	1, 3, 6 and 12 months after the beginning of the treatment

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Mahevas M, Audard V, Rousseau A, Cez A, Guerrot D, Verhelst D, Delahousse M, Hanrotel C, Pillebout E, Daugas E, Krastinova E, Valeyre D, Boffa JJ. Efficacy and safety of methylprednisolone pulse followed by oral prednisone versus oral prednisone alone in sarcoidosis tubulointerstitial nephritis. A randomized, open-label, controlled clinical trial. Nephrol Dial Transplant. 2022 Sep 6. pii: gfac227. doi: 10.1093/ndt/gfac227. [Epub ahead of print]

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: May 16, 2012
• First Submitted That Met QC Criteria: July 25, 2012
• First Posted (Estimate): July 30, 2012

Study Record Updates

• Last Update Posted (Estimate): February 25, 2016
• Last Update Submitted That Met QC Criteria: February 24, 2016
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Methylprednisolone; prednisone; renal sarcoidosis treatment
• Additional Relevant MeSH Terms: Lymphoproliferative Disorders; Lymphatic Diseases; Sarcoidosis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: P 110118; AOM 11003 (Other Identifier: Assistance Publique)