Condition category
Pregnancy and Childbirth
Date applied
26/03/2013
Date assigned
17/04/2013
Last edited
27/01/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Infection following miscarriage surgery is a problem affecting over 33 million pregnancies each year. A majority of women will have their miscarriage managed with surgery to empty the womb. Infection can occur following this surgery and this is a particular problem in low income countries. In some low income countries the rates of infection following miscarriage surgery are as high as 30%. These infections can result in death, serious illness or long-term health problems. Currently international and national medical guidelines do not recommend antibiotics to be given routinely in miscarriage surgery, because there is no evidence that tells us that this works. If antibiotics are given just before the procedure of miscarriage surgery this may reduce the chance of infection occurring. The aim of this study is to test this in four low income countries.

Who can participate?
Women who have suffered a miscarriage and are scheduled to have their miscarriage managed surgically, through an operation to empty their uterus.

What does the study involve?
Participants are offered either a single dose of prophylactic antibiotics (doxycycline and metronidazole) or an identical looking dummy pill (placebo), to be taken by mouth before the surgery. Participants are followed for 2 weeks after surgery to see if there is any difference in the rate of women developing pelvic infection. If any women show signs of infection they are given full treatment as soon as it is detected. The study also assess whether using antibiotics before surgery is cost effective.

What are the possible benefits and risks of participating?
Those women taking part in the study may benefit by having their health followed very carefully after the surgery. The study team also facilitate these women receiving prompt treatment if there are any problems. Even if participants do not benefit personally they study may help improve care for women in the future. Risks of taking part include the small risk of side effects from doxycycline or metronidazole, but these medications have been selected because they have a low risk of serious side effects such as allergy.

Where is the study run from?
The study is being managed and sponsored by the University of Birmingham (UK). The study sites are:
1. Malawi: Queen Elizabeth Central Hospital, Zomba Central Hospital and Kamuzu Central Hospital
2. Uganda: Mbale Regional Referral Hospital and Soroti Regional Referral Hospital
3. Tanzania: St Francis Hospital, Mwananyamala Hospital and Bagamoyo District Hospital
4. Pakistan: Aga Khan University Main Hospital, Hyderabad Hospital, Garden Hospital, Kharader Hospital and Karimabad Hospital

When is the study starting and how long is it expected to run for?
September 2013 to May 2017

Who is funding the study?
The Medical Research Council, the Wellcome Trust and the Department for International Development (UK)

Who is the main contact?
Dr David Lissauer
d.m.lissauer@bham.ac.uk

Trial website

http://www.aimstrial.org/

Contact information

Type

Scientific

Primary contact

Prof Arri Coomarasamy

ORCID ID

Contact details

School of Clinical and Experimental Medicine
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Type

Scientific

Additional contact

Dr David Lissauer

ORCID ID

Contact details

School of Clinical and Experimental Medicine
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RG_12-048

Study information

Scientific title

Effectiveness of antibiotic prophylaxis during surgical evacuation of the uterus for miscarriage management in low income countries: a multinational, randomised, double-blind placebo-controlled trial

Acronym

AIMS

Study hypothesis

To test the hypothesis that in women having miscarriage surgery, pre-surgery prophylactic antibiotics (oral doxycycline 400 mg and oral metronidazole 400 mg) reduces the risk of pelvic infection within 14 days of surgery.

Ethics approval

1. UK - Liverpool Ethics, 10/04/2013, protocol 13.15
2. Malawi - College of Medicine Research Ethics Committee, 11/10/2013, P.06/13/1393
3. Pakistan - Aga Khan University Research Ethics Committee, 11/11/2013, 2756-obs-erc-13
4. Pakistan - Drugs Regulatory Authority of Pakistan, 16/09/2014, F.6-1/2013
5. Tanzania - IHI IRB, 30/08/2013, IHI/IRB/no.25-2013
6. Tanzania - NIMRI, 01/11/2013, NIMRlHQ/R.8aJVol. IX/1652
7. Tanzania - TDFA, 04/08/2014, TFDAI4/CTR/001/03
8. Uganda - UNCST, 28/05/2014, HS 1400
9. Uganda - NDA, 06/12/2013, 347/ESR/NDA/DID-06/2013

Study design

Randomised double-blind placebo-controlled multi-national study with economic evaluation

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

http://www.aimstrial.org/patientinfo.aspx?lang=1

Condition

Infection, miscarriage, sepsis, antibiotic prophylaxis

Intervention

1. Doxycycline 400 mg oral and Metronidazole 400 mg oral, taken approximately 2 hours before the scheduled time of surgery
2. Placebo tablets of identical appearance and weight

Both the woman and health worker will not know which type of tablets they have been given. Participants are followed for 2 weeks after surgery to see if there is any difference in the rate of women developing pelvic infection. If any women show signs of infection they will be given full treatment as soon as it is detected. The study will also determine whether using antibiotics before surgery is cost effective.

Intervention type

Drug

Phase

Not Applicable

Drug names

Doxycycline, metronidazole

Primary outcome measures

Current primary outcome measures as of 27/01/2017:
Pelvic infection within 14* days of surgery, defined as two or more of:
1. Purulent vaginal discharge - on vaginal examination
2. Pyrexia >38.0°C - using a standardised tympanic thermometer
3. Tenderness on clinical examination
4. A white cell count >12x109/l , with no other recognised cause of infection
5. Or one of the above features, with the clinically identified need (following clinical assessment) to administer antibiotics for the treatment of presumed pelvic infection.
*In cases where participants do not return for follow up within this period, follow up until 28 days will be acceptable

Previous primary outcome measures:
Pelvic infection within 14 days of surgery, defined as two or more of:
1. Purulent vaginal discharge
2. Pyrexia >38.0°C
3. Uterine tenderness on examination and d) a white cell count >15x10^9 /l, with no other recognised cause of infection

Secondary outcome measures

Current secondary outcome measures as of 27/01/2017:
1. Secondary outcome measures:
Assessed at the follow-up appointment with a clinical assessment, history taking and reviewing available patient medical records:
1.1. Overall antibiotic use
1.2. Each component of the primary outcome
1.3. Death
1.4. Hospital admission
1.5. Unplanned consultations
1.6. Blood transfusion
1.7. Vomiting
1.8. Diarrhoea
1.9. Adverse events
1.10. Anaphylaxis and allergy
1.11. Duration of clinical symptoms (pain, additional analgesia, vaginal bleeding)
1.12. Days before return to usual daily activities
2. Outcomes for exploratory analyses:
2.1. Surgical complications
2.2. Full microbiological information, antibiotic sensitivities and any evidence of drug resistance will be collected where available
3. Resource use outcomes:
Resource use data will be prospectively collected to estimate the costs associated with the additional use of antibiotics in all participating centres in both arms of the trial. The main resources to be monitored include:
3.1. Additional staff time for explanation and dispensing of the medication
3.2. Type and grade of the health professional caring for each woman
3.3. Inpatient admissions and consultations (planned and unplanned)
3.4. Outpatient and emergency admissions and consultations
3.5. Unplanned further surgical interventions (e.g. curettage)
3.6. Additional investigation costs (e.g. ultrasounds)
3.7. Consumables (e.g. medication)
3.8. Resources used to manage surgery and treatment related complications (e.g. bleeding requiring transfusion)

Previous secondary outcome measures:
1. Secondary measures:
1.1. Death
1.2. Hospital admission
1.3. Unplanned consultations
1.4. Antibiotic use for presumed diagnosis of pelvic infection
1.5. Blood transfusion
1.6. Vomiting
1.7. Diarrhoea
1.8. Adverse events
1.9. Anaphylaxis and allergy
1.10. Duration of clinical symptoms (pain, additional analgesia, vaginal bleeding, days before return to usual daily activities)
2. Outcomes for exploratory analyses:
2.1. Surgical complications
2.2. Full microbiological information, antibiotic sensitivities and any evidence of drug resistance will be collected where available
3. Resource use outcomes: The main resources to be monitored include:
3.1. Additional staff time for explanation and dispensing of the medication
3.2. Type and grade of the health professional caring for each woman
3.3. Inpatient admissions and consultations (planned and unplanned)
3.4. Outpatient and emergency admissions and consultations
3.5. Unplanned further surgical interventions (e.g. curettage)
3.6. Additional investigation costs (e.g. ultrasounds)
3.7. Consumables (e.g. medication)
3.8. Resources used to manage surgery and treatment related complications (e.g. bleeding requiring transfusion)

Overall trial start date

01/09/2013

Overall trial end date

29/05/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Women with a spontaneous miscarriage (under 22 weeks gestation)
2. Women undergoing surgical evacuation of the uterus (by manual vacuum aspiration, suction curettage or sharp curettage)
3. Willing and able to give informed consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

3400

Participant exclusion criteria

1. Induced abortion of pregnancy
2. Septic miscarriage or evidence of infection
3. Allergy to either of the antibiotics
4. Current antibiotic use, or antibiotic use in the 7 days preceding surgical evacuation
5. Current febrile illness (temperature < 38oC)
7. Other contraindication to doxycycline or metronidazole use
8. Patient with condition requiring immediate care e.g. severe haemorrhage
9. Age less than 16 years

Recruitment start date

02/06/2014

Recruitment end date

30/04/2017

Locations

Countries of recruitment

Malawi, Pakistan, Tanzania, Uganda

Trial participating centre

Queen Elizabeth Central Hospital
-
Malawi

Trial participating centre

Zomba Central Hospital
-
Malawi

Trial participating centre

Kamuzu Central Hospital
-
Malawi

Trial participating centre

Mbale Regional Referral Hospital
-
Uganda

Trial participating centre

Soroti Regional Referral Hospital
-
Uganda

Trial participating centre

St Francis Hospital
-
Tanzania

Trial participating centre

Mwananyamala Hospital
-
Tanzania

Trial participating centre

Bagamoyo District Hospital
-
Tanzania

Trial participating centre

Aga Khan University Main Hospital
-
Pakistan

Trial participating centre

Hyderabad Hospital
-
Pakistan

Trial participating centre

Garden Hospital
-
Pakistan

Trial participating centre

Kharader Hospital
-
Pakistan

Trial participating centre

Karimabad Hospital
-
Pakistan

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

c/o Sean Jennings
Research Governance and Ethics Manager
Research Support Group
Room 119
Aston Webb Building
Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

Joint Global Health Trials Scheme

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Medical Research Council (UK), grant ref: MR/J009792/1

Alternative name(s)

MRC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Funder name

Wellcome Trust (UK), grant ref: 099943

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Funder name

Department for International Development (DfID) (UK)

Alternative name(s)

Department for International Development, UK, DFID

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Publication is planned in a high-impact peer reviewed journal within one year after the overall trial end date.

IPD sharing plan
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Intention to publish date

29/05/2018

Participant level data

Other

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

27/01/2017: The overall trial end date was changed from 01/03/2016 to 29/05/2017.