Feasibility and Acceptability of the Combination of Propess and AN24 Monica for Outpatient Labour Induction (PRAM)
Condition: Intrapartum Fetal Monitoring; Pregnancy
Study type: Observational

Summary: 
      In order to confirm the feasibility of home monitoring with Monica AN 24, a licensed portable
      device for measuring fetal and maternal electrocardiogram (ECG), and the feasibility of
      inpatient monitoring with Monica AN 24 in patients with Propess (a vaginal licensed drug
      delivery system used for induction of labour), we will perform a pilot study that will
      include 20 women in each arm.

      Feasibility of monitoring with Monica AN 24 both in hospital and at home will be confirmed in
      a pilot study. The success will be defined as at least 10 minutes of continuous satisfactory
      trace in any given hour in at least 80% of the patient.

      A main study will then be conducted to assess the feasibility and acceptability of the
      Propess and Monica AN24package of care for women undergoing induction of labour.

      The research questions are:

        1. Is outpatient induction with continuous monitoring technically feasible?

        2. Does the Propess and Monica AN24 care package of care provide adequate clinical
           information in line with the UK National Institute of Clinical Evidence (NICE) Guideline
           for Induction of labour?

        3. Is outpatient induction a concept that appeals to women?

        4. What do women consider to be the advantages and disadvantages of this package of care?

        5. What would women consider to be positive and/or negative outcome in future clinical
           trials of outpatient induction?

        6. Do fetuses with abnormal electrocardiogram (ECG) patterns have evidence of subclinically
           impaired cardiac function (feasibility study)?

        7. Do elevated concentrations of white blood cell components in the umbilical cord blood at
           birth influence fetal electrocardiogram (feasibility study)?
    

Detailed description: 
      Inclusion criteria

      Women with singleton pregnancy and cephalic presentation booked for induction of labour with
      unfavourable cervix (Bishop score <6) and normal pre-induction fetal monitoring.

      Low risk women in the context of this study include:

        -  Uncomplicated pregnancy requiring induction of labour after completed 37 weeks of of
           pregnancy with normal fetal assessment including:

             1. Social inductions/maternal requests

             2. Induction of labour for symphysis pubic dysfunction

             3. Obstetric Cholestasis

             4. Nonspecific Proteinuria (without any other medical problems)

        -  Parity < 4

        -  Intact membranes at study entry

        -  Living within a reasonable distance from the hospital (i.e., not more than approximately
           60 minutes driving time)

        -  Caregiver present at all times while at home

        -  Easy access to a safe method of transport for return to hospital

        -  Easy access to a telephone (either land line or mobile with good service)

        -  Agrees to remove the pessary herself following instructions in the patient leaflet

        -  Written informed consent

      Exclusion criteria

        -  Previous caesarean section

        -  Abnormal preinduction Cradiotocogram (CTG)

        -  Multiple pregnancy

        -  Fetal malformation or chromosomal abnormality

        -  Maternal age less than 18 years

        -  Contraindication to Propess induction

        -  Breech Presentation

        -  Foetal growth restriction

        -  Hypertension

        -  All Diabetics

      Recruitment

      In Liverpool Women's Hospital, women who have completed 37 weeks of Pregnancy and require
      induction of labour (as per inclusion/exclusion criteria above) while attending Antenatal
      clinic, delivery suite or the Obstetric Assessment Unit are offered management options. Women
      who have normal cardiotocogram (CTG), normal amniotic fluid volume and cephalic presentation
      confirmed by ultrasound, and who decide to have induction of labour will be approached by one
      of the investigators. The participant information sheet will be given to the woman, and
      participation in the study offered.

      Women who accept participation will be approached again when admitted to the Induction Suite
      1-3 days later. Women who labour spontaneously before induction day will be managed according
      to the standard hospital protocol and will not be asked to take part in the study.

      On admission to the Induction Suite the woman will be asked to sign the informed consent form
      and the eligibility of consenting women will be confirmed.

      Study progress

      Women who sign a consent form will have a Monica AN24 fetal monitor attached to the abdomen.
      Women will then follow the standard clinical protocol which includes:

        -  30 minutes of fetal heart rate monitoring (FHR). This must be reassuring to continue
           with the study;

        -  Prescription and administration of Propess

        -  A further 1 hour of FHR monitoring with the woman in a recumbent position in hospital

      If remote FHR monitoring cannot be established during initial assessment in the hospital,
      women will remain in hospital. If the in-hospital FHR signal is satisfactory, fetal
      monitoring will continue to be performed with Monica AN24 throughout her labour induction. If
      at any point the signal is deemed inadequate, standard CTG monitoring will be commenced.

      Women will be invited to complete a semi-structured diary throughout the outpatient episode
      of care. The woman's main supporter during labour (partner, mother, or friend) will also be
      invited to add comments in the diary. The diary will be collected on admission to hospital
      and placed in an opaque envelope. The diary will be collected by the Qualitative Team and
      will not be read by the clinicians/researchers involved in the clinical care.

      Women who meet all of the inclusion and none of the exclusion criteria and with a
      satisfactory in-hospital Monica AN24 signal will be taken through the instruction leaflets
      for the AN24 and Propess. If they are comfortable with both sets of instructions and the
      staff member believes they understand the study and how to handle an emergency situation,
      they will be allowed home. They will be advised that in case of research staff observing a
      suboptimal/non-reassuring fetal heart rate signal, they will be contacted by phone to come
      back to the hospital. Participating women will also be provided with a specially enabled
      mobile phone for the duration of their involvement with the study.

      The patient leaflets provided to women who are deemed suitable for home monitoring will
      include instructions to contact hospital staff and come back to the hospital in case of:

        1. vaginal bleeding

        2. painful uterine contractions requiring pain relief

        3. rhythmic, firm, uterine contractions occurring at a frequency of ≥ 3 in 10 minutes and
           lasting 45 seconds or more

        4. rupture of membranes

        5. Pessary falling out

      Women will be provided with the contact number for the Induction Suite (staffed 24/7), and
      they may contact the Induction Suite staff by telephone for reassurance at any time.

      The Monica AN24 monitoring will upload data to the central data base every 30 seconds via
      Bluetooth technology. The fetal heart rate and uterine activity pattern will be displayed on
      the PC monitor situated on the Induction Suite. This will be reviewed periodically by an
      experienced midwife as per standard hospital practice for women undergoing cervical ripening.

      Women will be told to return to the hospital in case of:

        1. Evidence of uterine hypertonus defined as a single contraction with duration of at least
           2 minutes

        2. Evidence of uterine tachysystole defined as at least 6 contractions in 10 minutes for 2
           consecutive 10 minute periods

        3. Non reassuring/pathological fetal heart rate (FHR)

        4. In case of regular uterine contractions (at least 3 in 10 minutes) the patient will be
           contacted by the midwife and asked if the contractions are painful. If the patient
           refers the contractions as non painful, home monitoring will be continued.

      Whilst the participant is at home, should a situation arise that the staff believes requires
      removal of the pessary (Propess), they will telephone the participant and instruct her to
      remove and dispose of the insert, and request that she should immediately return to the
      hospital. The staff member evaluating the situation will also determine whether emergency
      transport is required, i.e., ambulance, or whether car/taxi is acceptable.

      At 24 hours, assuming none of the above reasons for returning to hospital has occurred; women
      will be asked to return to hospital for removal of pessary and further assessment. Further
      management will be according to the standard hospital protocol for failed induction.

      Provided that the FHR signal from the Monica AN24 device is adequate, the device will be used
      for monitoring throughout the first stage of labour. In the second stage of labour a standard
      cardiotocogram (CTG) monitoring will be added.

      If at any point of the labour the signal is considered inadequate, standard cardiotocogram
      (CTG) monitoring will be provided.

      After birth, cord blood will be collected for analysis of lactates, cardiac enzymes,
      interleukin-6 (IL-6) and reactive protein C. These results will not be disclosed to the
      clinicians and will not influence subsequent management. Women will also be asked to give
      consent (optional) for one neonatal electrocardiogram (ECG) recording before hospital
      discharge if feasible.

      Women will also be asked to participate in a face to face interview after birth to determine
      their views on the outpatient care. This interview will be arranged by a member of the
      Qualitative Team after discharge from hospital and take place either at home or at hospital
      depending on the woman's wishes.
    

Intervention name(s): Dinoprostone; Monica AN 24
Intervention type(s): Drug; Device
Intervention description(s): Propess© vaginal delivery system consists of a non-biodegradable polymeric drug delivery device containing 10 mg Dinoprostone (PGE2) dispersed throughout its hydrogel matrix. The retrieval vaginal insert expands to twice its size and releases a continuous and predictable dose of Dinoprostone at a rate of approximately 0.3 mg/hr over 24 hours (4-5 mg PGE2 over 12 hours) in women with intact membranes whereas release is higher and more variable in women with premature rupture of membranes.; AN24 Monica is a portable, battery powered device designed to passively monitor a pregnant mother and unborn baby. The device is attached via a suitable cable assembly which in turn attaches to 5 standard disposable electrodes placed on the abdomen of a pregnant woman and is intended for use in either the home or hospital environment.
Other intervention name(s): Propess; CE0843
Intervention MeSH terms: Dinoprostone
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        In Liverpool Women's Hospital, women who have completed 37 weeks of Pregnancy and require
        induction of labour (as per inclusion/exclusion criteria above) while attending Antenatal
        clinic, delivery suite or the Obstetric Assessment Unit are offered management options.
        Women who have normal cardiotocogram(CTG), normal amniotic fluid volume and cephalic
        presentation confirmed by ultrasound, and who decide to have induction of labour were
        recruited.
      
Keywords: Induction of labour; Intraprtum fetal monitoring