Post-preeclampsia Renal Project: Study of Nephroprotection in Women Having Suffered Preeclampsia

Renal Alteration Clinical Trial

— RPPEC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01095939
• Other study ID #: 09-136
• Status: Completed
• Phase: Phase 3
• Start date: April 2010
• Est. completion date: March 2018

Study information

• Verified date: April 2018
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: March 2018
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Renal Alteration

Intervention

Drug:
• Placebo
Tablets; oral administration; once a day for 6 months. After this period of 6 months blinded treatment, the treatment will be stopped for 2 weeks. At the end of this washout period, a new renal evaluation is done. At that time, opened label treatment will be proposed to the women who still show renal alterations after a 2 weeks washout period
• Benazepril hydrochloride
Tablets (10 or 20 mg); oral administration; once a day for 6 months. After this period of 6 months blinded treatment, the treatment will be stopped for 2 weeks. At the end of this washout period, a new renal evaluation is done. At that time, opened label treatment will be proposed to the women who still show renal alterations after a 2 weeks washout period

Locations

Country	Name	City	State
Switzerland	Geneva University Hospitals	Geneva
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Geneva

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	microalbuminuria excretion rate (spot or 24h)		Baseline; 1 week + 24 weeks after treatment start
Primary	eGFR		Baseline; 1 week + 24 weeks after treatment start
Secondary	Filtration fraction %		Baseline; 1 week + 24 weeks after treatment start
Secondary	24h Ambulatory Blood Pressure	Mean; diurnal; nocturnal	Baseline; 1 week and 24 weeks after treatment start
Secondary	Effective Renal Plasma Flow		Baseline; 1 week and 48 weeks after treatment start
Secondary	Adverse Events		From signature of informed consent until last follow-up visit (36 months after treatment start)