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Indonesia Pravastatin to Prevent Preeclampsia Study (INOVASIA)

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ClinicalTrials.gov Identifier: NCT03648970
Recruitment Status : Recruiting
First Posted : August 28, 2018
Last Update Posted : August 28, 2018
Sponsor:
Information provided by (Responsible Party):
Muhammad Ilham Aldika Akbar, MD, OBGYN, Universitas Airlangga

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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 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 : March 1, 2018
Estimated Primary Completion Date : March 1, 2020
Estimated Study Completion Date : December 1, 2020

Resource links provided by the National Library of Medicine


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 Name: 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




Primary Outcome Measures :
  1. Preeclampsia [ Time Frame: From date of randomization until date of delivery ]
    Including preeclampsia, preeclampsia with severe features, and gestational hypertension.

  2. Preterm delivery [ Time Frame: 20 - 34 weeks, and 34 - 37 weeks ]
    Including indicated preterm delivery < 34 weeks and < 37 weeks

  3. 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


Secondary Outcome Measures :
  1. Perinatal outcome [ Time Frame: At delivery ]
    Gestational age at birth (days), birthweight (gram), birthweight percentile (INTERGROWTH), Apgar Score

  2. 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


Other Outcome Measures:
  1. 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)



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Ages Eligible for Study:   15 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03648970


Contacts
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Contact: Muhammad Ilham Aldika Akbar, MD, OBGYN +6281703270900 dokter_aldi@yahoo.com
Contact: Gustaaf Dekker, MD, PhD +61881829306 gustaaf.dekker@adelaide.edu.au

Locations
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Indonesia
Sanglah General Hospital Not yet recruiting
Denpasar, Bali, Indonesia
Contact: Ryan Saktika Mulyana, MD, OBGYN       ryanmul83@gmail.com   
Principal Investigator: Ryan Saktika Mulyana, MD, OBGYN         
Sub-Investigator: Evert Pangkahila, MD, OBGYN         
Dr. Moewardi Hospital Not yet recruiting
Surakarta, Central Java, Indonesia, 57126
Contact: Muhammad Adrianes Bachnas, MD, OBGYN    +628122692928    bachnasadri@gmail.com   
Principal Investigator: Muhammad Adrianes Bachnas, MD, OBGYN         
Sub-Investigator: Eric Edwin, MD, OBGYN         
Ramelan Naval Hospital Not yet recruiting
Surabaya, East Java, Indonesia, 60244
Contact: Agung Sunarko Putra, MD, OBGYN    +62811257852    dr.agung_sp@yahoo.com   
Principal Investigator: Agung Sunarko Putra, MD, OBGYN         
Sub-Investigator: Frans OH Prasetyadi, MD, OBGYN         
Dr. Soetomo Hospital Recruiting
Surabaya, East Java, Indonesia, 60285
Contact: Muhammad Ilham Aldika Akbar, MD, OBGYN    +6281703270900    dokter_aldi@yahoo.com   
Adam Malik General Hospital Not yet recruiting
Medan, North Sumatra, Indonesia
Contact: Dudy Aldiansyah       dudya141277@gmail.com   
Principal Investigator: Dudy Aldiansyah, MD, OBGYN         
Sub-Investigator: Makmur Sitepu, MD, OBGYN         
Dr. Wahidin Sudirohusodo General Hospital Not yet recruiting
Makasar, South Sulawesi, Indonesia
Contact: Deviana Soraya Riu, MD, OBGYN       virayariu@gmail.com   
Principal Investigator: Deviana Soraya Riu, MD, OBGYN         
Sub-Investigator: Ellen Theresia Wawengkang, MD, OBGYN         
Hasan Sadikin General Hospital Recruiting
Bandung, West Java, Indonesia
Contact: Muhammad Alamsyah Azis, MD, Obgyn       alamsyahaziz9119@gmail.com   
Principal Investigator: Muhammad Alamsyah Azis, MD, Obgyn         
Sub-Investigator: Johanes Cornelius Mose, MD, OBGYN         
Sponsors and Collaborators
Universitas Airlangga
Investigators
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Principal Investigator: Muhammad Ilham Aldika Akbar, MD, OBGYN Universitas Airlangga

Publications:

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Responsible Party: Muhammad Ilham Aldika Akbar, MD, OBGYN, Principal Investigator, MFM Consultant, Universitas Airlangga
ClinicalTrials.gov Identifier: NCT03648970     History of Changes
Other Study ID Numbers: IND012018
First Posted: August 28, 2018    Key Record Dates
Last Update Posted: August 28, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Muhammad Ilham Aldika Akbar, MD, OBGYN, Universitas Airlangga:
Preeclampsia
Pravastatin
Maternal morbidity
Neonatal mortality
Neonatal morbidity
Additional relevant MeSH terms:
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Pre-Eclampsia
Eclampsia
Hypertension, Pregnancy-Induced
Pregnancy Complications
Pravastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors