Condition category
Pregnancy and Childbirth
Date applied
15/01/2010
Date assigned
15/01/2010
Last edited
19/01/2010
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Ms Rebecca Scoble

ORCID ID

Contact details

Alliance Pharmaceuticals Ltd
Avonbridge House
Bath Road
Chippenham
SN15 2BB
United Kingdom
medinfo@alliancepharma.co.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

APL202-001

Study information

Scientific title

A randomised open comparision of intravaginal APL202 (25 or 50 µg) followed by 25 µg after 4 and 8 hours versus 3 mg of dinoprostone as a vaginal tablet followed by 3 mg after 6 hours in the induction of labour in nulliparous subjects

Acronym

Study hypothesis

The objective of study APL202-001 was to determine the safety and efficacy of APL202 in the induction of labour of nulliparous subjects compared with the standard agent currently used for cervical ripening.

The trial was previously registered at Pharmaceutical Industry Clinical Trials Database (ABPI/CMR) - https://www.cmrinteract.com/clintrial/default.htm.

Ethics approval

Huntingdon Research Ethics Committee approved on the 12th November 2004 (ref: 04/Q0104/94)

Study design

Randomised open comparative non-inferiority study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Induction of labour - nulliparous subjects only

Intervention

This was a randomised, open, comparative, non-inferiority study. Nulliparous subjects were allocated to one of two groups according to their Bishop score
values and then randomised to one of two treatments. Subjects with Bishop score values of less than or equal to 4 were allocated to Group 1 and randomised to receive one of the two treatments, APL202 or dinoprostone, as follows:
1. APL202 50 µg intravaginally followed by 25 µg intravaginally after 4 and 8 hours
2. Dinoprostone 3 mg intravaginally followed by 3 mg intravaginally after 6 hours

Subjects with Bishop score values less than 9 and greater than or equal to 5 were allocated to Group 2 and randomised to received one of the two treatments, APL202 or dinoprostone, as follows:
1. APL202 25 µg intravaginally followed by 25 µg intravaginally after 4 and 8 hours
2. Dinoprostone 3 mg intravaginally followed by 3 mg intravaginally after 6 hours

The statistical section of the APL202-001 protocol was amended during the course of the study to note that a two-sided analysis would be performed, in line with revised guidelines from the EMEA [Guideline on the choice of the non-inferiority margin, EMEA].

Subjects were randomised equally to each treatment with 506 subjects scheduled to be recruited in conjunction with the same number of subjects in a parallel study APL202-002 (506 were due to be randomised to each treatment). However, a decision was made in 2006 with the agreement of the ethics and regulatory authorities to pool the data from this study and study APL202-002. This meant that a combined total of 622 subjects, with not more than two-thirds and not less than one-third from either study, were required to be enrolled.

Scientific Contact Details - Lead Principal Investigator:
Mr Andrew Loughney MB BS, B Med Sci, PhD, MRCOG
Consultant Obstetrician and Head of Obstetrics
Women's Services
Royal Victoria Infirmary
Richardson Road
Newcastle upon Tyne, NE1 4LP
United Kingdom

Intervention type

Drug

Phase

Phase III

Drug names

APL202, dinoprostone

Primary outcome measures

Number of vaginal deliveries within 24 hours of the start of induction

Secondary outcome measures

1. Number of vaginal deliveries within 12 hours of the start of induction
2. Number of caesarean section deliveries
3. Mean induction-delivery interval
4. Distribution of induction-delivery interval
5. Oxytocin augmentation requirement
6. Number of instrument-assisted vaginal deliveries
7. Incidence and mean duration of tachysystole
8. Uterine hyperstimulation with fetal heart rate changes
9. Pyrexia during labour
10. Serious neonatal morbidity or perinatal death
11. Serious maternal morbidity or death

Measured at differing timepoints prior to the discharge of the patients from the hospital after the delivery of the baby.

Overall trial start date

06/01/2005

Overall trial end date

28/02/2007

Reason abandoned

Eligibility

Participant inclusion criteria

1. Subjects, aged 18 years or over, having at least one previous term pregnancy suitable for induction of labour with prostaglandin cervical ripening agents
2. Pregnancy duration of at least 37 weeks
3. Subjects with an unfavourable cervix defined as a Bishop Score of less than 9
4. Signed informed consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

622 participants

Participant exclusion criteria

1. Subjects requiring insulin to control their diabetes. Subjects with controlled Type II or gestational diabetes that did not require insulin could be included.
2. Subjects with a multiple pregnancy
3. Subjects in whom oxytocic drugs were generally contraindicated or where prolonged contractions of the uterus were considered inappropriate, i.e.:
3.1. History of caesarean section or major uterine surgery
3.2. Cephalopelvic disproportion
3.3. Foetal malpresentation
3.4. Clinical suspicion or definite evidence of pre-existing foetal distress
4. Subjects with an intercurrent vaginal, systemic or ascending infection
5. Subjects with clinical suspicion or definite evidence of placenta praevia or unexplained vaginal bleeding during their pregnancy. Occasional spotting, considered by the Investigator to be of no clinical significance concerning the use of cervical ripening agents and having a reasonable explanation (e.g. cervical ectropion, cervical polyps), was not a reason for exclusion.
6. Subjects with active cardiac, pulmonary, renal or hepatic disease
7. Subjects with abruptio placenta
8. Subjects with ruptured membranes
9. Subjects with a known allergy to prostaglandins or other constituents of the tablets
10. Subjects with any contraindication to vaginal delivery (e.g., active genital herpes)

Recruitment start date

06/01/2005

Recruitment end date

28/02/2007

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Alliance Pharmaceuticals Ltd
Chippenham
SN15 2BB
United Kingdom

Sponsor information

Organisation

Alliance Pharmaceuticals Ltd (UK)

Sponsor details

Avonbridge House
Bath Road
Chippenham
SN15 2BB
United Kingdom
+44 (0)1249 466966
info@alliancepharma.co.uk

Sponsor type

Industry

Website

http://www.alliancepharma.co.uk

Funders

Funder type

Industry

Funder name

Alliance Pharmaceuticals Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18715414

Publication citations

  1. Results

    Calder AA, Loughney AD, Weir CJ, Barber JW, Induction of labour in nulliparous and multiparous women: a UK, multicentre, open-label study of intravaginal misoprostol in comparison with dinoprostone., BJOG, 2008, 115, 10, 1279-1288, doi: 10.1111/j.1471-0528.2008.01829.x.

Additional files

Editorial Notes