Condition category
Pregnancy and Childbirth
Date applied
31/10/2010
Date assigned
10/01/2011
Last edited
07/05/2013
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

Prof Karim Abd-El-Maeboud

ORCID ID

Contact details

2 Mobarak St.
Off Asmaa fahmy
Ard El-Golf
Cairo
11341
Egypt
kabdelmaeboud@yahoo.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Assessment of efficacy and saftey of vaginal acidity enhancement with 3% acetic acid on response to vaginal misoprostol induction of abortion in missed mid-trimesteric abortion

Acronym

Study hypothesis

Enhacement of vaginal acidity induces cervical softening leading to more successful termination of pregnancy (TOP) with misoprostol along with shorter induction-abortion interval.

Ethics approval

The Ethics and Research Committee of Obstetrics and Gynaecology Department, Faculty of Medicine, Ain Shams University approved in September 2010

Study design

Randomised controlled single centre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details below to request a patient information sheet

Condition

Termination of pregnancy (TOP)

Intervention

This trial took place at Ain Shams University Maternity Hospital. The participants will be randomly allocated to the following two groups:
1. Group I: Subjects (n = 24) who will be treated with acidifying vaginal gel (acetic acid 3%) applied every 12 hours, starting 2 days ahead of the planned procedure
2. Group II: Subjects (n = 24) who will be treated with neutral (placebo) vaginal gel (the base of the gel without active agent) applied every 12 hours, starting 2 days ahead of the planned procedure

During the pre-selection visit, exclusion and inclusion criteria will be applied. When the patient's consent is obtained, the investigator will receive the medication package with a label carrying the corresponding number. Baseline investigations - ABO and rhesus blood group, complete blood count (CBC), random blood sugar, serum glutamate oxalate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum creatinine, and coagulation profile will be done. The investigators will supervise application of the medication (dose by dose) from the package carrying the number matching with the patient's entry number. The biometrician will keep the sealed envelopes with the numbers of order till the end of the study. The medication will be strictly allocated in the numbers order, according to the randomization plan. The randomization schedule will be constructed so that the number in each group would be balanced for every 10 women recruited. Subjects withdrawn from the study before the onset of uterine pains will not be substituted. The next patient included in the study will receive the next number.

Before digital vaginal examination, a speculum examination will be performed and vaginal pH value will be measured by using indicator paper (pH-indicator strips pH 0-14 Universal indicator paper, Merck KGbA, Darmstadt, Germany). The indicator will be held with an artery forceps against the vaginal wall –in the midvagina- until it becomes wet. Then, another indicator paper will be held with an artery forceps against the vaginal wall - high up in the vagina - until it becomes wet. Colour change of the strip will be immediately compared with the colorimetric scale and the measurement of vaginal pH at the two positions, mid and high vagina, will be recorded. Digital vaginal examination will be then performed assessing three criteria only. These are dilatation, length, position (posterior, midway, anterior or central), and consistency (firm or soft).

After pretreatment with the vaginal gel for two days, induction of abortion will performed, starting at 8 am. Peri-abortion prophylaxis will entail metronidazole 1 g rectally at the time of abortion plus doxycycline 100 mg orally twice daily for 7 days, commencing on the day of abortion. All women will receive misoprostol 800 mg vaginally, then misoprostol 400 mg vaginal, 4-hourly, to a maximum of five doses in the first 24 hours. Before inserting the tablet in the posterior fornix, it will be wetted with acetic acid (7%) to assure its complete dissolution. If a woman does not have adequate uterine contractions within 8 hours following the last dose, the same regimen will be repeated over the following 24 hours and if no response was achieved, this will be considered a failure of therapy, and alternative interventions (treatment with high-dose oxytocin, administration of extra-amniotic prostaglandin F2á, mechanical cervical dilatation with a 16-French Foley balloon catheter or performing a hysterotomy) are to be carried out on the basis of judgment of the clinicians.

Vital signs of the patients including temperature, pulse rate, blood pressure and the frequency of uterine contractions will be monitored every 3 h, with a recording of the time of the onset of regular uterine contractions, and the time of the expulsion of conceptus. Pethidine hydrochloride 50 mg will be given for pain relief if women requested. After abortion, the products of conception (fetus and placenta) will be examined to see whether the abortion was complete, Evacuation of the uterus will be performed under general anaesthesia only if the placenta is found to be incomplete. The amount of blood loss during abortion will be assessed clinically. After abortion, oxytocin 50 U/ 1000 mL normal saline will be administered intravenously at the rate of 100 mL/h. The side-effects of misoprsotol therapy, including nausea, vomiting, diarrhea, fever and marked abdominal pain, will be recorded. Anti-D immunoglobulin G (250 iu before 20 weeks of gestation and 500 iu thereafter) will be given, by injection into the deltoid muscle, to all non-sensitized RhD negative women within 72 hours following termination. The abortus will be handled to the pathologist for further study.

Following termination of pregnancy, women will be given a written account of the symptoms they may experience and a list of those that would make an urgent medical consultation necessary. They will be given a 24-hour telephone helpline number to use if they feel worried about pain, bleeding or high temperature. Urgent clinical assessment and emergency gynaecology admission will be available when necessary. Also, each woman will be offered a follow-up appointment within 2 weeks of the termination. On discharge, each woman will be given a letter that includes sufficient information about the procedure, with referral for further genetic counseling if necessary. Future contraception will be discussed before discharge following termination.

Intervention type

Drug

Phase

Not Applicable

Drug names

Acetic acid (3% gel), misoprostol

Primary outcome measures

Efficacy will be assessed on the basis of improved cervical softening as evidenced by success of induction and its duration. The main outcome measures are
1. Successful abortion rate (defined as expulsion of fetus within 12, 24 and 48 h after administration of misoprsotol)
2. Induction-to-abortion interval (defined as the duration between the application of the first dose of misoprsotol and the time of the expulsion of the fetus)
3. The total dose of misoprsotol used

Secondary outcome measures

1. Drug tolerability as judged by the investigator will be collected and analyzed
2. Side-effects of misoprostol, including vomiting, diarrhoea, fever (defined as a single temperature reading exceeding 38°C), marked abdominal pain along with the need for analgesic and its total dose
3. Blood loss will be estimated visually by the attending obstetrician and excessive bleeding will be defined as an estimated blood loss of 500 ml or more
4. The rate of incomplete abortion (the need for surgical evacuation of the uterus)

Overall trial start date

10/11/2010

Overall trial end date

10/03/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 18 - 40 years
2. Missed abortion
3. Singleton pregnancy
4. Gestational age ranging between 14 and 26 weeks of pregnancy (by calculation, examination and/or ultrasound)
5. Uterus and cervix apparently normal on clinical examination
6. Cervix not dilated with absence of effacement
7. Absence of uterine activity
8. Written and signed informed consent by the patient to participate in the study

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

48

Participant exclusion criteria

1. A contraindication to medical termination of pregnancy, e.g. placenta praevia
2. Evidences suggesting onset of spontaneous abortion (uterine contractions with or without cervical changes)
3. Presence of vaginal bleeding
4. Presence of intrauterine contraceptive device (IUCD) in situ
5. Presence of ruptured membranes and/or suspicion of septic abortion as evidenced by maternal temperature of 38°C or more, uterine tenderness or foul-smelling vaginal discharge
6. Previous trial to induce abortion or the use of pre-induction agent during the current pregnancy
7. Any contraindication to receiving prostaglandins, including known hypersensitivity to misoprostol or other prostaglandins (PGs), history of asthma, glaucoma, cardiac or cardiovascular disease
8. Parity six or more
9. Multifetal pregnancy
10. Polyhydramnios
11. Uterine anomaly, previous two or more caesarean sections, previous uterine surgery, e.g., myomectomy or trauma, e.g., uterine perforation
12. History of any cervical surgery or manipulation: cervical cerclage during current pregnancy history thereof during a previous pregnancy, previous cauterization of cervical erosion, previous cervical dilatation or operation with resultant apparent cervical tears or lacerations
13. Associated collagen or autoimmune medical disorder
14. Metabolic acidosis as a result of a medical disorder
15. History of adverse effects to vaginally administered medications
16. Likelihood of requiring treatment during the study period with drugs not permitted by the study protocol which include all vaginal forms of medications
17. Mental condition rendering the patients unable to understand the nature, scope and possible consequences of the study

Recruitment start date

10/11/2010

Recruitment end date

10/03/2011

Locations

Countries of recruitment

Egypt

Trial participating centre

2 Mobarak St.
Cairo
11341
Egypt

Sponsor information

Organisation

Ain Shams University Maternity Hospital (Egypt)

Sponsor details

c/o Prof Karim H I Abd-El-Maeboud
Abbassia
Cairo
11566
Egypt
obsgyn.asu@gmail.com

Sponsor type

Hospital/treatment centre

Website

http://med.shams.edu.eg/index.php

Funders

Funder type

Hospital/treatment centre

Funder name

Ain Shams University Maternity Hospital (Egypt)

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

2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22980429

Publication citations

  1. Results

    Abd-El-Maeboud KH, Ghazy A, Ibrahim A, Hassan N, El-Bohoty A, Gamal-El-Din I, Vaginal acidity enhancement with a 3% acetic acid gel prior to misoprostol treatment for pregnancy termination in the midtrimester., Int J Gynaecol Obstet, 2012, 119, 3, 248-252, doi: 10.1016/j.ijgo.2012.06.017.

Additional files

Editorial Notes