Sildenafil citrate effect on in vivo human trophoblast research

ISRCTN ISRCTN36718005
DOI https://doi.org/10.1186/ISRCTN36718005
EudraCT/CTIS number 2017-001878-42
Secondary identifying numbers 11
Submission date
02/07/2017
Registration date
13/07/2017
Last edited
12/07/2017
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Pregnancy and Childbirth
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
The placenta is an organ attached to the lining of the womb during pregnancy. It keeps the unborn baby's (fetus) blood supply separate from the mother’s blood supply, and provides a link between the two. Problems can occur during the development of the placenta that can cause the blood flow to the fetus to be too low (placental insufficiency). Sildenafil citrate is a drug which could be used to improve the development of the placenta. Early results show an improvement in blood flow and fetus weight but a failure to delay premature birth. The aim of this study is to assess sildenafil citrate's effect early in pregnancy in order to find the best time to give the drug to prevent placental insufficiency.

Who can participate?
Healthy pregnant women between 20-40 years old during the first trimester of pregnancy who are coming to hospital for a legal medical abortion

What does the study involve?
The participants undergo an ultrasound exam to assess the blood flow in the placenta, and are then randomly allocated to take either sildenafil citrate or a placebo (dummy drug). The participants stay in the waiting room for one hour before a second ultrasound scan is performed. Blood pressure and heart rate are measured every 15 minutes and any side effects are recorded. Participants are also contacted by telephone to record any side effects 12 hours later and 7 days after legal abortion has been carried out. Placental tissue samples are also taken.

What are the possible benefits and risks of participating?
Participants are informed that there are unlikely to be any direct benefits from participating, but the information obtained from this study may help to improve treatment for future patients. The studies of sildenafil in animals, non-pregnant adults, pregnant women and unborn babies have not shown harmful effects. It is not possible to say that sildenafil is 100% safe, but based on what is known it is unlikely that the use of sildenafil in pregnancy harms the patient or the baby. Sildenafil has been used in pregnant women and premature babies previously and no side effects have been reported in babies. However, people taking sildenafil can have some short-lasting side effects like headache, flushing, blurred vision and indigestion.

Where is the study run from?
Consorcio Hospital General Universitario (Spain)

When is the study starting and how long is it expected to run for?
September 2017 to June 2018

Who is funding the study?
La Fundación Investigación Hospital General Universitario de Valencia (Spain)

Who is the main contact?
Prof. Maria Begoña Pellicer

Contact information

Prof Maria Begoña Pellicer
Scientific

Servicio de Ginecologia y Obtetricia , pabellon C, planta baja, secretaria Ginecologia.
Avenida Tres Cruces nº 2
Valencia
46014
Spain

ORCiD logoORCID ID 0000-0002-8981-8444

Study information

Study designRandomized double-blind placebo-controlled longitudinal study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typePrevention
Participant information sheet Not available in web format, please use contact details to request a participant information sheet
Scientific titleSildenafil citrate placental effect evaluated by ultrasound: a randomised controlled trial
Study acronymSC pregnancy
Study objectivesSingle dose of sildenafil citrate in pregnant women during 1st trimester improves vascular flow in placental territory.
Ethics approval(s)Ethics Committee of Consorcio Hospital General Universitari de Valencia (Spain) - approval pending
Health condition(s) or problem(s) studiedPlacental vascular flow
InterventionOnce the patients have been properly advised about the study and the consent form has been signed as a part of their agreement, patients are sent to the hospital to undergo an initial ultrasound exam by the obstetrics doctor in charge or the fellow in training. Transvaginal ultrasound scan will be performed using a Voluson E6 (GE Medical Systems, Zipf, Austria) and a four-dimensional 6–9 MHz transvaginal probe. It is optional to the patient to see the fetus during the scan if they want to. Randomization will be performed using sealed envelopes by a clinician who does not belong to the research group. Patients are randomly assigned to two groups:
Group A (n=30) receive 5mg folate acid as a placebo
Group B (n=30) receive 50 mg sildenafil citrate

Patients will stay in the waiting room for one hour before a second ultrasound scan is performed. The trialsts calculate the three 3D power Doppler ultrasound vascular indices, the vascularization index (VI), flow index (FI) and vascularization flow index (VFI), the calculation is based on and related to the total and relative amounts of power Doppler information within the volume of interest. VI denotes the ratio of color-coded voxels to all voxels within the volume and is expressed as a percentage, FI represents the mean power Doppler signal intensity from all color-coded voxels and VFI is the simple mathematical relationship derived from multiplying VI by FI and dividing the result by 100. Both FI and VFI are unit less and are expressed as a numerical value ranging from 0 to 100. The indices are thought to reflect the number of vessels within the volume of interest (VI), the intensity of flow at the time of the 3D sweep (FI), and both blood flow and vascularization.

Blood pressure and maternal heart rate is measured every 15 minutes and side effects are recorded. Patients are also contacted by telephone to record side effects 12 hours later and 7 days after legal abortion has been carried out. After abortion has been practised in the referred centre placental tissue samples (n= 10) from each studied group containing trophoblast tissue will be obtained and processed in order to examine angiogenic factors and histologic structure.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Sildenafil citrate
Primary outcome measurePlacental vascular flow, measured by standard vascular indexes acquired with three dimensional angiopower doppler output when the patient is admitted and one hour later (following drug or placebo administration)
Secondary outcome measures1. Uterine artery hemodynamic flow effect, measured using an automated semiquantitative analysis of Doppler spectra before and 1 hour after Sildenafil oral administration
2. Maternal blood pressure, measured using an automated oscillometric blood pressure measurement device before and during one hour (every 15 minutes) after Sildenafil oral administration
3. Maternal heart frequency, calculated automatically using waveform spectra before and 1 hour after Sildenafil oral administration
Overall study start date01/09/2017
Completion date30/06/2018

Eligibility

Participant type(s)Healthy volunteer
Age groupAdult
SexFemale
Target number of participantsControl group (n=30), treated group (n=30)
Key inclusion criteria1. Healthy women between 20-40 years old
2. Confirmed pregnant viability without any obstetric complication
3. First trimester gestational age
4. Coming to hospital for legal medical abortion
Key exclusion criteria1. Obstetric risk factors: recurrent miscarriage, previous preeclamsia and hematology disease
2. Current use of vasoactive drugs (mainly related to hypertension treatment)
3. Toxic substances abuse
4. Threatened abortion symptoms
5. Sildenafil citrate contraindications, as are described in the prescribing information formulary (excluding pregnancy)
Date of first enrolment01/09/2017
Date of final enrolment01/09/2018

Locations

Countries of recruitment

  • Spain

Study participating centre

Consorcio Hospital General Universitario de Valencia
Avenida Tres Cruces, 2
Valencia
46014
Spain

Sponsor information

Servicio Ginecologia y Obstetricia Hospital General de Valencia
Hospital/treatment centre

Avenida Tres Cruces, 2
Valencia
46014
Spain

Website http://chguv.san.gva.es
ROR logo "ROR" https://ror.org/03sz8rb35

Funders

Funder type

Hospital/treatment centre

Fundation Investigation Hospital General Universitari Valencia CIF G-96.792.221

No information available

Results and Publications

Intention to publish date30/06/2019
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planPlanned publication in a high-impact peer reviewed journal.
IPD sharing planThe datasets generated during and/or analysed during the current study are/will be available upon request from Dr Ander Morales Vicente.