Clinical trial NCT01095939: Post-preeclampsia Renal Project: Study of Nephroprotection in Women Having Suffered Preeclampsia
Official title: A Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy and Safety of Benazepril (ATC N° C09AA07) in the Treatment of Persistent Renal Dysfunction in Pre-eclamptic Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Renal Alteration
Keywords: Renal function consecutive to pre-eclampsia
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2010-03-30
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the Post-preeclampsia Renal Project is to investigate the renal function of preeclamptic women after delivery, and to determine whether the anti-hypertensive drug named benazepril efficiently improves the dysfunctions observed.

Detailed description: Several epidemiological studies suggest that the risk of death from cardiovascular causes among women with preeclampsia may be increased, and that preeclampsia contrary to what has been long thought, is not cured with delivery. Preeclampsia has long been considered a 2-stage disease, stage one corresponding to an impaired placental perfusion resulting from abnormal spiral artery remodeling, and stage two corresponding to the maternal manifestations of disease, characterized by hypertension and proteinuria. However, preeclampsia might include an additional, 3rd stage, that of the post-partum period (Gammill \& Roberts, 2007) This phase deserves to be investigated. In particular, it is crucial to determine whether the changes that occur in renal hemodynamics during preeclampsia are reversible after more than 6 weeks, and whether PEC women are salt-sensitive after delivery.

The link between chronic kidney disease and cardiovascular mortality is well established. An independent, graded association exists between a reduced GFR and the risk of death, cardiovascular events, and hospitalization (Go et al, 2004). Besides, salt-sensitivity is associated with an increased cardiovascular and renal risk (Franco \& Oparil, 2006). The Renal Post PEC study aims at establishing if the renal dysfunctions that occur in PEC women can be reversed by the administration of inhibitors of the renin-angiotensin system that are known to improve cardiovascular and renal risk profiles in hypertensive patients. By virtue of their potent renal vasodilatory properties and favourable remodelling of the GBM, ACE inhibitors may improve salt-sensitivity, endothelial function, renal plasma flow and GFR, and general renal prognosis in women who experienced from preeclampsia.

Eligibility criteria: Pre-selection Criteria:

* Normotensive women with no proteinuria before the 20th week of gestation AND
* Women with hypertension (BP ≥140/90 mm Hg) and proteinuria (≥ 0.3 g /24h or 2++ dipstick) after the 20th week of gestation

Inclusion Criteria:

* Clearance of creatinine ≤ 80 ml/min (Gault et Cockcroft)
* Serum creatinine ≥ 80 µmol/L
* Microalbuminuria comprised between 30 and 300 mg/d and/or a urinary spot with microalbuminuria/creatinine ratio ≥ 3.5 and/or macroalbuminuria (24h urinary albumin excretion ≥ 0.500 mg)
* BP ≥ 140/90 mm Hg OR ongoing antihypertensive treatment
* CRP ≥ 4 mg/dL

Exclusion Criteria:

* Those unlikely to co-operate in the study
* Those who refuse to use appropriate contraceptive measures during the treatment period (intrauterine device, oral contraceptives, condom, diaphragm)
* Those with a history of pre-term delivery
* Those with known history of severe allergic reaction
* Those who consume drugs
* Aged \< 18 years old

Primary outcomes:
measure: microalbuminuria excretion rate (spot or 24h)
timeFrame: Baseline; 1 week + 24 weeks after treatment start
measure: eGFR
timeFrame: Baseline; 1 week + 24 weeks after treatment start
Secondary outcomes:
measure: Filtration fraction %
timeFrame: Baseline; 1 week + 24 weeks after treatment start
measure: 24h Ambulatory Blood Pressure
timeFrame: Baseline; 1 week and 24 weeks after treatment start
measure: Effective Renal Plasma Flow
timeFrame: Baseline; 1 week and 48 weeks after treatment start
measure: Adverse Events
timeFrame: From signature of informed consent until last follow-up visit (36 months after treatment start)
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Geneva University Hospitals
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
Study officials:
affiliation: University Hospital, Geneva
name: Antoinette Pechère
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ditisheim A, Wuerzner G, Ponte B, Vial Y, Irion O, Burnier M, Boulvain M, Pechere-Bertschi A. Prevalence of Hypertensive Phenotypes After Preeclampsia: A Prospective Cohort Study. Hypertension. 2018 Jan;71(1):103-109. doi: 10.1161/HYPERTENSIONAHA.117.09799. Epub 2017 Nov 13.