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

Cholesterol Embolism Systemic Clinical Trial

— MECCORT  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01452100
• Other study ID #: 1003701
• Secondary ID: 2010-021467-33
• Status: Terminated
• Phase: Phase 2
• First received: September 15, 2011
• Last updated: May 6, 2016
• Start date: June 2011
• Est. completion date: December 2015

Study information

• Verified date: May 2016
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 39
• Est. completion date: December 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cholesterol Embolism Systemic
• Embolism

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:
• 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).

Locations

Country	Name	City	State
France	CHU Toulouse service néphrologie	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Toulouse	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

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