Efficacy of Prednisone in Patients With Severe Systemic Atheroembolism (Cholesterol Cristal Embolism) (MECCORT)

Cholesterol cristal embolization (CCE) is an orphan multisystem vascular condition occurring in elderly with severe atherosclerosis.

In most patients, avoiding the precipitating factors and combination of statin and RAS inhibitor are recommended.

The lack of randomized controlled trial in CCE precludes significant advances. The investigators decided to assess whether prednisone started early, at mild dosage and for a short period prevents death and progression to end-stage renal failure in patients with severe CCE, as compared to placebo.

Study Overview

• Status: Terminated
• Conditions: Cholesterol Embolism Systemic
• Intervention / Treatment: Drug: prednisone; Other: placebo

Detailed Description

Erosion of atheromatous plaque results in release of cholesterol crystal embolism that ultimately occlude medium-sized arterioles and capillaries of the kidney, skin, gastrointestinal tract and central nervous system. The diagnosis relies on histopathological demonstration of cholesterol cristal embolism in any target organ, or can be assumed if the 3 following criteria are met (1) presence of one or more precipitating factors (2) renal function deterioration in atherosclerotic patients (3) ischemic changes of the extremities or demonstration of retinal CCE. Despite the dismal prognosis in multisystem CCE mortality the optimal treatment remains unknown.

In most patients, avoiding the precipitating factors and combination of statin and RAS inhibitor are recommended. The benefit of prednisone is uncertain, but its dramatic impact has been underlined in several short retrospective series, even with moderate daily dosage (0,2-0,5 mg/kg). However, adverse side effects of steroid therapy in uremic elderly with CCE have not been assessed. In addition, the optimal duration of the treatment has not been assessed. The lack of randomized controlled trial in CCE precludes significant advances. The investigators decided to assess whether prednisone started early, at mild dosage and for a short period prevents death and progression to end-stage renal failure in patients with severe CCE, as compared to placebo.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31052
    • CHU Toulouse service néphrologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Biopsy-proven CCE or clinically diagnosed CCE as assessed on the 3 following criteria : presence of one or more precipitating factors renal function deterioration in atherosclerotic patients ischemic changes of the extremities or demonstration of retinal embolism
• Severe CCE as defined by either acute renal failure (S creatinine > 125 micromol/l and increase > 25 % of baseline), or severe abdominal changes (hemorrhage, infarction, perforation or weight loss > 5 % of body weight) or severe central nervous system neurological complication

Exclusion Criteria:

• CCE unproven, or restricted to one organ, or non-active contraindication to prednisone.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: prednisone; • Patients enrolled into the study will be treated with prednisone, 20 mg/day (if body weight <70 kg ; or 25mg/d if body weight >70 kg) for 1 month, then tapered to 12.5 mg/d (month 2) and 7.5 mg/d (month 3) and stop. In both groups, patients will be treated according to expert advice including use of statins (according to French Health Agency recommendation), a RAS inhibitor and supportive treatment (including nutrition, treatment of heart failure, and dialysis).	Drug: prednisone; Patients enrolled into the study will be treated with prednisone, 20 mg/day (if body weight <70 kg ; or 25mg/d if body weight >70 kg) for 1 month, then tapered to 12.5 mg/d (month 2) and 7.5 mg/d (month 3) and stop. In both groups, patients will be treated according to expert advice including use of statins (according to French Health Agency recommendation), a RAS inhibitor and supportive treatment (including nutrition, treatment of heart failure, and dialysis).; Other Names: Cortancyl
Placebo Comparator: placebo; Patients enrolled into the study will be treated with placebo, 20 mg/day (if body weight <70 kg ; or 25mg/d if body weight >70 kg) for 1 month, then tapered to 12.5 mg/d (month 2) and 7.5 mg/d (month 3) and stop. In both groups, patients will be treated according to expert advice including use of statins (according to French Health Agency recommendation), a RAS inhibitor and supportive treatment (including nutrition, treatment of heart failure, and dialysis).	Other: placebo; • Patients enrolled into the study will be treated with placebo, 20 mg/day (if body weight <70 kg ; or 25mg/d if body weight >70 kg) for 1 month, then tapered to 12.5 mg/d (month 2) and 7.5 mg/d (month 3) and stop. In both groups, patients will be treated according to expert advice including use of statins (according to French Health Agency recommendation), a RAS inhibitor and supportive treatment (including nutrition, treatment of heart failure, and dialysis).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1-year survival and 1-year renal survival (composite criteria)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and duration of hospitalization(s)	Number and duration of hospitalization(s)	1 year
course of renal function	stable, deterioration or improvement of serum creatinine - defined by changes > 20 % compared to base line	1 year
number of cardiovascular events	acute coronary syndrome, stroke, heart failure, critical lower member ischemia, digestive ischemia	1 year
prednisone tolerance	as regard to de novo diabetes mellitus, and severe psychiatric or infectious episode (requiring hospitalization).	1 year

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Collaborators: Ministry of Health, France
• Investigators: Study Director: Dominique Chauveau, PhD, University Hospital, Toulouse; Principal Investigator: Antoine Huart, MPD, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: September 15, 2011
• First Submitted That Met QC Criteria: October 13, 2011
• First Posted (Estimate): October 14, 2011

Study Record Updates

• Last Update Posted (Estimate): May 9, 2016
• Last Update Submitted That Met QC Criteria: May 6, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: embolism; creatinine; renal insufficiency; prednisone; cholesterol cristal; systemic atheroembolism
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Embolism, Fat; Embolism; Embolism, Cholesterol; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: 1003701; 2010-021467-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No