Clinical trial NCT01452100: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cholesterol Embolism Systemic
Keywords: embolism
cholesterol cristal
creatinine
renal insufficiency
prednisone
systemic atheroembolism
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2011-10-14
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 1-year survival and 1-year renal survival (composite criteria)
timeFrame: 1 year
Secondary outcomes:
measure: Number and duration of hospitalization(s)
timeFrame: 1 year
measure: course of renal function
timeFrame: 1 year
measure: number of cardiovascular events
timeFrame: 1 year
measure: prednisone tolerance
timeFrame: 1 year
Other outcomes:
Locations:
city: Toulouse
country: France
facility: CHU Toulouse service néphrologie
Study officials:
affiliation: University Hospital, Toulouse
name: Dominique Chauveau, PhD
role: STUDY_DIRECTOR
affiliation: University Hospital, Toulouse
name: Antoine Huart, MPD
role: PRINCIPAL_INVESTIGATOR
References: