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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Alteration
• Intervention / Treatment: Drug: Placebo; Drug: Benazepril hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland
    • Geneva University Hospitals
  • Lausanne, Switzerland
    • Centre Hospitalier Universitaire Vaudois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Arm	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
Experimental: Benazepril	Drug: 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; Other Names: Lotensin; Cibacen; ATC: C09AA07

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
microalbuminuria excretion rate (spot or 24h)	Baseline; 1 week + 24 weeks after treatment start
eGFR	Baseline; 1 week + 24 weeks after treatment start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Filtration fraction %		Baseline; 1 week + 24 weeks after treatment start
24h Ambulatory Blood Pressure	Mean; diurnal; nocturnal	Baseline; 1 week and 24 weeks after treatment start
Effective Renal Plasma Flow		Baseline; 1 week and 48 weeks after treatment start
Adverse Events		From signature of informed consent until last follow-up visit (36 months after treatment start)

Collaborators and Investigators

• Sponsor: University Hospital, Geneva
• Investigators: Principal Investigator: Antoinette Pechère, University Hospital, Geneva

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: March 29, 2010
• First Submitted That Met QC Criteria: March 29, 2010
• First Posted (Estimate): March 30, 2010

Study Record Updates

• Last Update Posted (Actual): May 1, 2018
• Last Update Submitted That Met QC Criteria: April 30, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Renal function consecutive to pre-eclampsia
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Benazepril
• Other Study ID Numbers: 09-136

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No