INOVASIA: Indonesia Pravastatin to Prevent Preeclampsia Study

Sponsor

Universitas Airlangga (Other)

Overall Status

Unknown status

CT.gov ID

NCT03648970

Collaborator

(none)

280

Enrollment

Locations

Arms

33.1

Anticipated Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

BACKGROUND Preeclampsia is a major cause of maternal and neonatal morbidity worldwide. There is currently no cure for preeclampsia, the only definitive treatment is termination of pregnancy by induction of labour or caesarean section. Statin has been proposed to represent a new approach to improve disease outcome/prevent preeclampsia based on its multilayered activity toward pregnancy protection, including: protection of vascular endothelial cells survival, induce expression of heme oxygenase 1 (HO-1), inhibiting the release of soluble FMS-like tirosine kinase-1 (sFlt-1) and soluble endoglin (sEng), two main culprits in the pathophysiology of preeclampsia.

OBJECTIVE The aim of this study is to observe the effect of pravastatin administration in patients with high risk of preeclampsia in order to reduce maternal and neonatal mortality and morbidity.

METHODS This is a prospective randomized controlled clinical trial. The research will be held in 5 maternal fetal medicine centers in Indonesia (multicenter study). The recruitment will be done by permuted block random sampling methods, with sample size around 280 patients divides into two group. Patients with high risk of preeclampsia will be randomized either to get pravastatin 2 x 20 mg per oral and aspirin 1 x 80 mg (treatment group) or low dose aspirin only (control group). The patient will be followed regularly until delivery to obtain detailed maternal and neonatal outcome.

OUTCOME Primary Outcomes: Maternal preeclampsia, severe preeclampsia, gestational hypertension, indicated preterm delivery less than 37 weeks, indicated preterm delivery less than 34 weeks, maternal complications, length of hospital stay, and any serious adverse event.

Secondary Outcomes: Composite fetal/neonatal mortality and morbidity (stillbirth, neonatal death, respiratory distress syndrome, intracerebral hemorrhage, neonatal sepsis, intra uterine growth restriction [Small for Gestational Age (SGA) < 5th centile], and necrotizing enterocolitis), birthweight, birthweight percentile, level of care (well baby, intermediate, NICU), NICU length of stay, ventilator usage, and length of perinatal hospital stay.

KEYWORDS: pravastatin, preeclampsia, neonatal mortality, neonatal morbidity

Condition or Disease	Intervention/Treatment	Phase
Pre-Eclampsia	Drug: Pravastatin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

280 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Multicenter Randomized Non Blinded Trial comparing low dose aspirin versus low dose aspirin and pravastatin in patients with high risk developing preeclampsiaMulticenter Randomized Non Blinded Trial comparing low dose aspirin versus low dose aspirin and pravastatin in patients with high risk developing preeclampsia

Masking:

Single (Outcomes Assessor)

Masking Description:

The diagnosis is made by resident unaware of the medication patients received

Primary Purpose:

Prevention

Official Title:

Pravastatin to Prevent Preeclampsia and Reduce Maternal-Neonatal Mortality and Morbidity in High Risk Preeclampsia Patients

Actual Study Start Date :

Mar 1, 2018

Anticipated Primary Completion Date :

Mar 1, 2020

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pravastatin Treatment Group In this arm, the participant will be given aspirin 80 mg daily per oral and the study drugs, Pravastatin 2 x 20 mg per oral daily.	Drug: Pravastatin The participant will be given pravastatin 2 x 20 mg per oral daily Other Names: Pravastatin Sodium
No Intervention: Control Group In this arm, the participant will be given aspirin 80 mg daily per oral and the study drugs, Pravastatin 2 x 20 mg per oral daily. In this arm, the participant will be given aspirin 80 mg daily per oral, as it already a standard protocol for the high risk preeclampsia group

Arm

Intervention/Treatment

Experimental: Pravastatin Treatment Group

In this arm, the participant will be given aspirin 80 mg daily per oral and the study drugs, Pravastatin 2 x 20 mg per oral daily.

Drug: Pravastatin

The participant will be given pravastatin 2 x 20 mg per oral daily

Other Names:

Pravastatin Sodium

No Intervention: Control Group

In this arm, the participant will be given aspirin 80 mg daily per oral and the study drugs, Pravastatin 2 x 20 mg per oral daily. In this arm, the participant will be given aspirin 80 mg daily per oral, as it already a standard protocol for the high risk preeclampsia group

Outcome Measures

Primary Outcome Measures

Preeclampsia [From date of randomization until date of delivery]
Including preeclampsia, preeclampsia with severe features, and gestational hypertension.
Preterm delivery [20 - 34 weeks, and 34 - 37 weeks]
Including indicated preterm delivery < 34 weeks and < 37 weeks
Maternal complication [From date of randomization until date of delivery]
Any maternal complication caused by preeclampsia: eclampsia, seizure, HELLP syndrome, acute pulmonary edema, acute kidney injury, Cardivascular accident, liver failure, sepsis, and pneumonia

Secondary Outcome Measures

Perinatal outcome [At delivery]
Gestational age at birth (days), birthweight (gram), birthweight percentile (INTERGROWTH), Apgar Score
Composite neonatal morbidity and mortality [At delivery]
stillbirths, neonatal death, respiratory distress syndrome, intracerebral hemorrhage, neonatal sepsis, necrotizing enterocolitis, length NICU admission, and length of stay

Other Outcome Measures

The side effect of Pravastatin [Up to 6 month after birth]
Including adverse reactions, Serious Adverse Event (SAE), and Suspected Unexpected Serious Adverse Reaction (SUSAR)

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Gestational Age 10 wk - 19 wk 6 day
History of previous preeclampsia requiring birth < 37 weeks (risk 30%), or
Patients with a combination of at least 2 major risk factors plus an abnormal uterine artery Doppler at 11-20 weeks gestation (risk preeclampsia 30%):
Major clinical risk factors (Obesity, strong family history of preeclampsia [mother or sister], maternal age > 40 years old, chronic hypertension, Policystic Ovarian Syndrome (PCOS), Chronic kidney disease, diabetes mellitus, multiple pregnancies, first pregnancy, pregnancy interval more than 10 years, new partner/husband, Reproductive technologies (IVF pregnancy), heritable thrombophilias, Booking Blood pressure >130/80 mmHg, family history of early onset cardiovascular disease, lower socioeconomic status)
Abnormal uterine artery Doppler defined as (Second trimester screening:

average resistance index > 0.58 and/or or early-diastolic diastolic notch. First trimester screening: Pulsatility index > 95th centile or PI > 1.5) or:

First trimester screening (11+0 to 14+1 weeks): Combination of maternal risk factors, elevated MAP, and increased Uterine artery pulsatility index (UTPI).
Second trimester screening (19+0 to 24+6 weeks): Combination of maternal risk factors, elevated MAP, and increased Uterine artery pulsatility index (UTPI).
Combination of elevated mean arterial pressure (MAP > 90 mmHg) in the second trimester with abnormal uterine artery Doppler
Combination elevated booking blood pressure (> 130/85 mmHg) with abnormal uterine artery Doppler
Live fetus, no detectable fetal anomaly

Exclusion Criteria:

Condition where the pregnancies should be terminated within 48 hours, on the basis of any indication (patients consume pravastatin less than 2 days).
Contraindication to the statin use:
Hypersensitivity to pravastatin
Active liver disease
Pre pregnant renal insufficiency/kidney failure (history of hemodialysis)
Current use of statin
Participation in any other controlled trial of investigational medical products in pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanglah General Hospital	Denpasar	Bali	Indonesia
2	Dr. Moewardi Hospital	Surakarta	Central Java	Indonesia	57126
3	Ramelan Naval Hospital	Surabaya	East Java	Indonesia	60244
4	Dr. Soetomo Hospital	Surabaya	East Java	Indonesia	60285
5	Adam Malik General Hospital	Medan	North Sumatra	Indonesia
6	Dr. Wahidin Sudirohusodo General Hospital	Makasar	South Sulawesi	Indonesia
7	Hasan Sadikin General Hospital	Bandung	West Java	Indonesia