Indonesia Pravastatin to Prevent Preeclampsia Study (INOVASIA)

August 23, 2018 updated by: Muhammad Ilham Aldika Akbar, MD, OBGYN, Universitas Airlangga

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

280

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Indonesia
    • Bali
      • Denpasar, Bali, Indonesia
        • Not yet recruiting
        • Sanglah General Hospital
        • Contact:
        • Principal Investigator:
          • Ryan Saktika Mulyana, MD, OBGYN
        • Sub-Investigator:
          • Evert Pangkahila, MD, OBGYN
    • Central Java
      • Surakarta, Central Java, Indonesia, 57126
        • Not yet recruiting
        • Dr. Moewardi Hospital
        • Contact:
        • Principal Investigator:
          • Muhammad Adrianes Bachnas, MD, OBGYN
        • Sub-Investigator:
          • Eric Edwin, MD, OBGYN
    • East Java
      • Surabaya, East Java, Indonesia, 60244
        • Not yet recruiting
        • Ramelan Naval Hospital
        • Contact:
        • Principal Investigator:
          • Agung Sunarko Putra, MD, OBGYN
        • Sub-Investigator:
          • Frans OH Prasetyadi, MD, OBGYN
      • Surabaya, East Java, Indonesia, 60285
        • Recruiting
        • Dr. Soetomo Hospital
        • Contact:
    • North Sumatra
      • Medan, North Sumatra, Indonesia
        • Not yet recruiting
        • Adam Malik General Hospital
        • Contact:
        • Principal Investigator:
          • Dudy Aldiansyah, MD, OBGYN
        • Sub-Investigator:
          • Makmur Sitepu, MD, OBGYN
    • South Sulawesi
      • Makasar, South Sulawesi, Indonesia
        • Not yet recruiting
        • Dr. Wahidin Sudirohusodo General Hospital
        • Contact:
        • Principal Investigator:
          • Deviana Soraya Riu, MD, OBGYN
        • Sub-Investigator:
          • Ellen Theresia Wawengkang, MD, OBGYN
    • West Java
      • Bandung, West Java, Indonesia
        • Recruiting
        • Hasan Sadikin General Hospital
        • Contact:
        • Principal Investigator:
          • Muhammad Alamsyah Azis, MD, Obgyn
        • Sub-Investigator:
          • Johanes Cornelius Mose, MD, OBGYN

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

11 years to 41 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preeclampsia
Time Frame: From date of randomization until date of delivery
Including preeclampsia, preeclampsia with severe features, and gestational hypertension.
From date of randomization until date of delivery
Preterm delivery
Time Frame: 20 - 34 weeks, and 34 - 37 weeks
Including indicated preterm delivery < 34 weeks and < 37 weeks
20 - 34 weeks, and 34 - 37 weeks
Maternal complication
Time Frame: 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
From date of randomization until date of delivery

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The side effect of Pravastatin
Time Frame: Up to 6 month after birth
Including adverse reactions, Serious Adverse Event (SAE), and Suspected Unexpected Serious Adverse Reaction (SUSAR)
Up to 6 month after birth

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitas Airlangga

Investigators

  • Principal Investigator: Muhammad Ilham Aldika Akbar, MD, OBGYN, Universitas Airlangga

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2018

Primary Completion (Anticipated)

March 1, 2020

Study Completion (Anticipated)

December 1, 2020

Study Registration Dates

First Submitted

August 22, 2018

First Submitted That Met QC Criteria

August 23, 2018

First Posted (Actual)

August 28, 2018

Study Record Updates

Last Update Posted (Actual)

August 28, 2018

Last Update Submitted That Met QC Criteria

August 23, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IND012018

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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