A new study examining the link between a bacterial signature and preterm birth is set to benefit the millions of infants and families worldwide who will potentially suffer from this complication of pregnancy.
The Preterm Birth Prevention Study will look at the presence of specific bacteria in the vagina in mid pregnancy to identify women who are likely to deliver early.
The clinical trial was being carried out in Perth to see if treating GLU positive women at 14-20 weeks’ gestation with antibiotics reduces the rate of spontaneous preterm birth.
The Preterm Birth Prevention Study aims to enrol 6174 pregnant Western Australian women from Perth’s public maternity hospitals.
If successful, this testing and treatment program would be a major breakthrough in pregnancy care and would likely save the lives of hundreds of Western Australian infants and many more around the world.
- Premature (preterm) birth – delivery before 37 weeks’ gestation - is a major obstetric problem affecting around 8% of all deliveries in Australia. Babies born very preterm can suffer from a number of serious and life-threatening health problems, many of which can persist well into the later years of life.
- One of the major causes of preterm birth (PTB) is bacterial infection of the uterus (womb), which is present in 20-40% of cases of PTB, especially those where birth occurs at 32 weeks’ of gestation or less. Previous research has indicated that several bacterial species can cause PTB. However, many of these bacteria are also part of the normal healthy microbial community found in the vagina in pregnancy.
- Unfortunately, attempts to identify women who are likely to deliver a preterm baby based on the presence of specific bacteria in the vagina have not been very successful to date. This is in part because the types of bacterial communities found in different women are complex and can vary considerably, making a diagnosis of PTB risk based upon this very difficult.
- However, after six years of research, our team has developed a new diagnostic test called the ‘GLU’ test (patent pending), which, based upon our preliminary data, may be useful for identifying women at risk of giving birth preterm. The GLU test looks for the presence of three specific bacteria in a self-collected vaginal swab sample. Each of the three types of bacteria are quite common and are not indicative of an infection or abnormality, so ordinarily would not be treated with antibiotics. A woman must test positive to all three of these bacteria in the same sample to be diagnosed “GLU-positive”.
- This clinical trial is being carried out in Perth to see if treating GLU positive women at 14-20 weeks’ gestation with antibiotics reduces the rate of spontaneous PTB. Antibiotics have been shown in other trials to be modestly effective in preventing PTB, but until now there has not been an effective way of identifying women who are truly at risk and would benefit from treatment.
- Information derived from this study will help to confirm whether the GLU test is useful for predicting risk of PTB due to bacterial infection and whether this risk can be reduced with treatment with antibiotics and probiotics.
- This is a phase three randomised clinical trial, designed to determine the effectiveness of treating pregnant women with antibiotics and probiotics to prevent preterm birth based on the presence of a bacterial signature (GLU test) performed on self-collected vaginal swab samples taken before 20 weeks’ gestation. We aim to enrol 6174 pregnant Western Australian women to this study from Perth’s public maternity hospitals.
- All participants in the study will collect their own swab for analysis; half of the study participants will be placed into the intervention group and half will be placed into the control group. Only GLU positive women in the intervention group will receive treatment. The decisions as to which group you are placed in will be done using a computerised randomisation process after sample collection. The trial will be able to compare the effects of targeted treatment verses current standard care on PTB rates and neonatal outcomes.
- This study will help us confirm that the GLU test is a useful tool for predicting women who are at an increased risk of spontaneous PTB. In addition, the study will allow us to see if we can reduce the risk of PTB in GLU positive women through a simple treatment program that could easily be implemented into standard antenatal obstetric practice. If successful, this testing and treatment program would be a major breakthrough in pregnancy care and would likely save the lives of hundreds of Western Australian infants and many more around the world.
- The research team is led by Professor John Newnham, a world renowned maternal-fetal medicine expert based at KEMH. The team also includes Professor Jeff Keelan, Dr Matthew Payne and Professor Dorota Doherty. The team are experts in the area of infection-associated PTB and have conducted multiple studies in this area before. Funding for this research is being provided by the National Health and Medical Research Council of Australia, who undertook an extensive review of the project before approving funding.
You will be asked to supply a vaginal swab sample for the GLU test and complete a short questionnaire. Your further involvement in the study will depend on which group you are randomised to and the result of your GLU test.
- If you are in the control group then you need to do nothing else after providing your vaginal swab and will not be contacted again by the research team. You will continue to receive the current standard obstetric care provided by your obstetric care provider.
- If you are in the intervention group and you test GLU positive you will need to participate in an antibiotic/probiotic treatment program. If you test GLU negative, then nothing else needs to be done and you will continue to receive the current standard obstetric care provided by your obstetric care provider.
- Women who test GLU positive will receive a phone call from one of the study midwives within seven days of being recruited. The midwife will describe what is involved in taking part in the treatment program and check that there are no current medical contraindications.
- A treatment pack will be prepared for you by the KEMH pharmacy, and you will need to return to KEMH to collect this from the outpatient dispensary area on the lower ground floor of B block. KEMH pharmacy staff will explain how to use the medications at the time of collection, along with how to keep track of medication usage in the logbook provided. Participants will also be provided with the phone number of the KEMH Pharmacy and one of the study midwives in case any additional information or advice is needed during the treatment program.
- Briefly, the treatment program consists of taking one oral antibiotic tablet (250 mg Azithromycin) each day for seven days, combined with applying an antibiotic cream (2% Clindamycin, commonly known as Dalacin V) vaginally, once daily, for the same period of time. After the antibiotic therapy, in order to help restore healthy vaginal bacteria, participants will be asked to apply a vaginal probiotic tablet (Canesflor) before bedtime, once daily for a week, then once per week for another four weeks. The entire treatment program lasts for six weeks. The Azithromycin tablets will be supplied in 500mg size, with a defined break-point in the middle of the tablet. In order to take a 250mg dose, you will need to carefully break the tablets in two, take one half, and then store the second half in the packaging until the next day.
- At the completion of the treatment program three pre-labelled swabs, along with a questionnaire on the study, will be mailed to participants together with a self-addressed express post envelope to return them in. The medication logbook used to record daily use of study medications will also be returned at this time. These swabs will be delivered to our laboratory for follow-up analysis to see if the treatment program was successful. The follow-up swabs will be analysed after the recruitment and delivery stage of the trial, so participants won’t be informed of the results before the birth of their child; women will then continue to receive standard obstetric care from their healthcare provider and their delivery outcomes will be recorded.
- By participating in this study you will be providing valuable data needed to validate a diagnostic test (GLU) that has the potential to accurately detect women at a high risk of giving birth preterm. In addition, if you test GLU positive and are in the intervention group, you will be helping us work out if we can prevent PTBs that originate from vaginal infection though a simple, low-risk treatment program. If successful, this test and treatment program is likely to prevent many PTBs and save the lives of hundreds of Western Australian infants.
- As with all studies involving pharmacological treatment, there are risks, although the risks in this study are low. The collection of vaginal swabs is a simple, routine procedure and poses no real risk to yourself or your infant.
- For GLU positive women in the intervention group, the antibiotics prescribed are widely used in pregnancy and are safe and well-tolerated. Side effects of azithromycin are uncommon, particularly at the 250 mg dose (half the standard dose). Mild gastrointestinal symptoms (e.g. diarrhoea, nausea and abdominal pain) are the most likely side effects.
- A range of other adverse effects have been reported, although these are very rare. They include: Oral thrush; vaginal thrush; dizziness; headaches; fatigue; muscle or joint aches; development of a rash; ringing in the ears; and an altered sense of taste and smell. Major side-effects are even rarer, particularly at the dose being prescribed in this trial, but may include: severe persistent diarrhoea; irregular heartbeat; symptoms of sun burn; decreased skin sensitivity; skin rash; widespread body rash, fever and swollen lymph nodes; aggressiveness, agitation and/or anxiety; bleeding or bruising more readily than normal; severe chills, sore throat and/or mouth ulcers; dark urine or blood in urine/bowel movements; and severe upper stomach pain.
- 2% Clindamycin vaginal cream is also safe and well-tolerated with only minor, usually temporary side-effects. These include: vaginal irritation; vaginal itching; vaginal discharge; headache; vertigo; heartburn; dizziness; nausea; constipation; diarrhoea; stomach pain; rash; hives (itchy rash); redness of the skin; pain when urinating; pelvic pain; back pain; altered taste; bad breath; and flatulence. Major side-effects are extremely rare, but include: severe stomach cramps; watery and severe diarrhoea (which may also be bloody); and fever.
- You will be provided with a copy of the consumer medicine information sheet for both drugs which list all known side-effects, and can call one of the study midwives directly if you have any concerns.
- Probiotics are considered very safe in pregnancy. They typically contain selected types of bacteria called Lactobacilli which are able to help promote a healthy vaginal environment and exclude colonisation by bad bacteria. The probiotic being used in this study (Canesflor) has been shown to be particularly effective at protecting against thrush and bacterial vaginosis.
- The study midwives will ensure women in the treatment program are not taking any medications that may clash with the two antibiotics before treatment is prescribed.
If you would like any more information about this study, please do not hesitate to contact one of the research team. They are very happy to answer your questions.
Who to contact if you have any concerns/complaints about the study or its organisation?
- Professor John Newnham, Maternal-Fetal Medicine Specialist, 6458 1331
- Professor Jeff Keelan, Head of Laboratories, 6458 1880
- Dr Matthew Payne, Research Fellow, 6488 7970
- Professor Dorota Doherty, Head of WIRF Biostatistics Unit, 6458 1627
If you have any concerns or complaints regarding this study, you can contact the Director of Medical Services at KEMH (Telephone No: (08) 6458 2222). Your concerns will be drawn to the attention of the Ethics Committee who is monitoring the study.