Clinical trial NCT02888639: Pharmacoepidemiological Study of Secondary Hyperparathyroidism in Lorraine
Official title: EPHEYL: Étude PHarmacoÉpidémiologique de l'hYperparathyroïdie Secondaire en Lorraine
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: ESRD
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2016-09-05
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: ESRD requiring mainteance dialysis

Brief summary: The pharmacoepidemiological EPHEYL (Étude PHarmacoÉpidémiologique de l'hYperparathyroïdie secondaire en Lorraine) study is a 2-year, open-cohort, prospective, observational study on incident SHPT, i.e. newly diagnosed, with a 2 year follow-up, set in the 12 dialysis units located in the French region of Lorraine (public or private).

Detailed description: In the early stages of the disease, 90% of patients with chronic renal failure present evidence of bone remodeling due to secondary hyperparathyroidism (HPT). As the disease progresses and patients require dialysis for end-stage renal failure (ESRF), the incidence of secondary HPT declines to 25-40% with reduced bone remodeling as shown by osteomalacia observed in 4-12% of patients and adynamic bone in 20-40%. Observational studies have described an association between serum phosphorus level, phosphorus-calcium product, parathormone (PTH) level, and mortality. Since there is no real consensus, treatments, basically diet and drugs, are tailored to each individual. The therapeutic range is wide and interactions are frequent. Therapeutic efficacy is compromised by the variability of PTH assay results, the ambulatory nature of interventions, and poor patient adherence. The guidelines issued in 2003 stipulate that corrective measures, i.e. dietetic counseling with or without drug therapy, are needed when serum PTH exceeds 300 pg/ml. When the PTH level exceeds 500, or even more so 800 pg/ml, HPT can constitute an indication for parathyroid surgery or calcimimetic treatment.

Data from a randomized comparison between cinacalcet and surgery are lacking. The evidence-based decision for surgery is made conjointly by the nephrologist, the surgeon and the patient, limiting the feasibility of randomization. Parathyroidectomy can be achieved by three techniques whose efficacy has been studied in historical observational studies. Cinacalcet received marketing approval in 2004 for "the treatment of secondary HPT in patients with ESRF treated by dialysis. Mimpara can be used in the context of a regimen including phosphate chelators and/or vitamin D analogs, as needed". Four double-blind studies have demonstrated the efficacy of cinacalcet versus placebo in decreasing the PTH level, but there is no proof of the efficacy of cinacalcet in terms of cardiovascular events and mortality. One cost-effectiveness study showed that parathyroidectomy was superior to cinacalcet, except if the patient was on dialysis for a short period before renal transplantation or presented contraindications for surgery.

While randomized trials are the gold standard, such trials include a limited number of patients for a limited period of time. This does not enable an observation of long-term practices and adverse effects. Moreover, such trials do not concern patients with other co-morbid conditions taking several drugs, in particular, elderly subjects. The concept of the pharmacoepidemiological study is to describe real-life populations taking a given drug, using both quantitative and qualitative parameters to determine efficacy, risk, and drug use in real-life conditions free of the constraints of a clinical trial.

ÉPHÉYL is an observational pharmacoepidemiological study concerning the prescription of calcimimetic agents and parathyroidectomy in patients with ESRF on dialysis who present severe secondary HPT (PTH ≥ 500 pg/ml). The aim is to describe indications and efficacy: control of PTH, calcium and phosphorus serum levels within their recommended ranges, patient tolerance of the therapeutic interventions, and the cost of such interventions, as well as patients' adhesion to treatment and their self-assessed quality-of-life. This three-year inclusion study, based on the Lorraine REIN registry, will involve all participants in the Néphrolor network. The study will begin on April 1st, 2009.

Eligibility criteria: Inclusion Criteria:

* age \>= 18 years
* Patient on hemodialysis or peritoneal dialysis for 3 months or more in one of the 12 dialysis units in the study.
* Patient included in the REIN registry in the Lorraine region.
* Parathormone greater than or equal to 500 pg / ml for the first time after 01/04/2009 (patient incident for secondary hyperparathyroidism).

Exclusion Criteria:

* age \< 18 years.
* Patient living in Lorraine but dialysed in a unit outside Lorraine.
* Diagnosis of secondary hyperparathyroidism with higher parathormone or equal to 500 pg / ml placed before 1/4/2009.
* Patient who have received medical treatment with cinacalcet or by surgical parathyroidectomy for secondary hyperparathyroidism.
* Patient expressing opposition to the collection of information.

Primary outcomes:
measure: Parathormone level
timeFrame: 2 years
Secondary outcomes:
measure: Phosphocalcium product level
timeFrame: 2 years
measure: Serum calcium level
timeFrame: 2 years
measure: Serum phosphorus level
timeFrame: 2 years
measure: Symptoms and / or clinical events caused by hyperparathyroidism
timeFrame: 2 years
measure: Tolerance of therapeutic interventions: nausea, vomiting, diarrhea, hypocalcemia
timeFrame: 2 years
measure: The quality of life
timeFrame: 2 years
measure: Satisfaction of professionals
timeFrame: 2 years
measure: The direct costs of treatment
timeFrame: 2 years
measure: Patient compliance
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
affiliation: CHRU de Nancy
name: Luc Frimat, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Filipozzi P, Ayav C, Ngueyon Sime W, Laurain E, Kessler M, Brunaud L, Frimat L. Trajectories of CKD-MBD biochemical parameters over a 2-year period following diagnosis of secondary hyperparathyroidism: a pharmacoepidemiological study. BMJ Open. 2017 Mar 27;7(3):e011482. doi: 10.1136/bmjopen-2016-011482.