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

• ClinicalTrials.gov Identifier: NCT01452100
• Recruitment Status: Terminated
• First Posted: October 14, 2011
• Last Update Posted: May 9, 2016
• Sponsor: University Hospital, Toulouse
• Collaborator: Ministry of Health, France
• Information provided by (Responsible Party): University Hospital, Toulouse

Tracking Information

• First Submitted Date: September 15, 2011
• First Posted Date: October 14, 2011
• Last Update Posted Date: May 9, 2016
• Study Start Date: June 2011
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 13, 2011): 1-year survival and 1-year renal survival (composite criteria) [ Time Frame: 1 year ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 13, 2011)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of Prednisone in Patients With Severe Systemic Atheroembolism (Cholesterol Cristal Embolism)
• Official Title: Efficacy of Prednisone in Patients With Severe Systemic Atheroembolism (Cholesterol Cristal Embolism)

Brief Summary

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.

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Cholesterol Embolism Systemic

Intervention

• 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 Name: Cortancyl
• 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).

Study Arms

• 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).
  Intervention: Drug: prednisone
• 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).
  Intervention: Other: placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 6, 2016): 39
• Original Estimated Enrollment (submitted: October 13, 2011): 140
• Actual Study Completion Date: December 2015
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT01452100
• Other Study ID Numbers: 1003701; 2010-021467-33 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University Hospital, Toulouse
• Study 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

• PRS Account: University Hospital, Toulouse
• Verification Date: May 2016