Clinical Trial Details
— Status: Unknown status
Administrative data
| NCT number |
NCT00133926 |
| Other study ID # |
353577 |
| Secondary ID |
NHMRC Australia |
| Status |
Unknown status |
| Phase |
Phase 2
|
| First received |
August 23, 2005 |
| Last updated |
April 4, 2007 |
| Start date |
March 2005 |
| Est. completion date |
June 2008 |
Study information
| Verified date |
April 2007 |
| Source |
King Edward Memorial Hospital |
| Contact |
John P Newnham, MD, FRANZCOG |
| Phone |
61 9 9340 1331 |
| Email |
jnewnham[@]obsgyn.uwa.edu.au |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The aim of the study is to investigate, in an Australian population of pregnant women,
whether the treatment of periodontal disease during pregnancy prevents pre-term birth and
other complications of pregnancy. Dental screening and periodontal treatment protocols have
been based on standard techniques employed by hygienists that can be readily applied to the
general obstetric population.
Description:
HYPOTHESES
Primary Hypothesis:
That treatment of periodontal disease during pregnancy reduces the rate of pre-term birth
from 12% to 7%.
Secondary Hypothesis:
That treatment of periodontal disease during pregnancy reduces the rate of:
- Fetal growth restriction.
- Complications of pre-term birth including respiratory distress syndrome.
- Periodontal disease measured at 36 weeks gestation.
Research Plan Synopsis:
A randomized controlled trial is being conducted with recruitment of women from the antenatal
clinics of Perth’s major obstetric centres and associated private practices. The sample is
being enriched by inviting women with a history of poor oral health or pre-term birth. 5400
eligible women will undergo a hygienist-based screening study at 12-20 weeks gestation. 1094
women who meet the criteria for periodontal disease determined from our recent pilot study
will be allocated at random to the treatment or control groups. Those in the treatment group
will receive three one-hour hygienist-based periodontal treatment sessions commencing at 20
weeks gestation, followed by re-examination at 26 weeks. Re-treatment will be offered to the
5% of cases in which treatment has been ineffective, and ongoing maintenance to the
remainder. Women allocated to the control group will be offered similar treatment after
completion of the pregnancy.
RESEARCH PLAN
Study Design:
Multi-centered single-blinded randomized controlled trial conducted within the metropolitan
area of Perth, Western Australia. The obstetric and newborn health care providers are blinded
to the periodontal treatment allocation.
Inclusion Criteria:
Women with single pregnancies at 12 to 20 weeks gestation with periodontal disease defined as
periodontal pocketing at a threshold of 4mm or more at 10% or more of sites and who agree to
receive periodontal treatment are eligible. The definition of periodontal disease is based on
the published literature and our pilot study designed to determine the prevalence in our
local obstetric population. Periodontal pocketing is used to define the presence of
periodontal disease rather than clinical loss of attachment because it better represents the
microbial challenge and is the most frequently employed criterion. In our pilot study, 15% of
our general unselected population met this criterion.
Exclusion Criteria:
Women are ineligible if they are: unable to attend for periodontal treatment; less than 16
years of age; present for antenatal care after 20 weeks gestation; are unable to understand
the implications of participation in the trial; have a fetus with a known abnormality that
would predispose the pregnancy to pre-term birth such as those that may cause polyhydramnios;
have a multiple pregnancy; have cardiac disease that would require antibiotic therapy for
dental treatment; are currently receiving periodontal treatment; or have fewer than 20 teeth.
Trial Entry:
All women planning to attend the antenatal clinics at King Edward Memorial Hospital (KEMH) in
Perth, Western Australia are provided with written information about the trial with their
appointment letter. Those attending other public antenatal clinics and a proportion of
private practices also receive the information and invitation. Women who do not have
exclusion criteria are invited by a research midwife to provide written informed consent to
undergo a periodontal examination. After the examination those women who meet the criteria
for periodontal disease are invited by a member of the research team to participate in the
trial and to provide written informed consent to have treatment. A questionnaire is
administered to obtain data on demographic and medical factors that may influence oral health
and details of past and present dental care. Women who are found to not have periodontal
disease are asked to provide consent for their obstetric outcomes to be retrieved from the
state-wide computerized data collection system that encompasses all births in Western
Australia.
Randomisation:
Each woman is allocated to the treatment or control group by the sealed-envelope technique,
prepared in blocks of 20. Recruitment is stratified by history of pre-term birth, nulliparity
and smoking practice. Women who smoke in either arm of the study are provided with written
material encouraging them to cease smoking.
Management of the Treatment Group:
Women allocated to the treatment group are given appointments to attend the Oral Health
Centre of Western Australia (OHCWA).
Management of the Control Group:
Women allocated to the control group are provided with the findings of their periodontal
examination to take to their dentist and written information on oral health care. Each woman
is also invited to receive free dental care at OHCWA commencing 6 weeks after delivery and
continuing for 16 weeks, as described below.
Dental Examination:
The simple screening dental examination is a modified WHO CPITN (Gjermo,1998) conducted in a
well-equipped dental room within the antenatal clinic at KEMH. This examination takes
approximately 20 minutes and is conducted by a study hygienist under supervision by the study
periodontists. If periodontitis is detected the woman is invited to participate in the trial
as described previously.
Periodontal Treatment:
Treatment Group:
All periodontal treatment is conducted in the Oral Health Centre of Western Australia
(OHCWA), located 2 km from KEMH. A full periodontal examination is first performed using a
constant force automated Florida probe (Florida Probe Corporation, Gainesville, Florida, USA)
which provides precise measurements of pocket depth to 0.2mm, and stores data directly into a
computer. This measurement system has been used in our pilot study and two separate probes
and computer systems are available for this trial. Further periodontal parameters are
recorded, including clinical attachment loss, full mouth bleeding after probing, and modified
O’Leary Plaque Index. Treatment explanation is then provided by the hygienist and consent
confirmed. The treatment plan for each woman is determined in consultation with a study
periodontist and is conducted over 3 visits each of one hour duration. These treatments
consist of non-surgical debridement of the sub- and supra-gingival plaque, removal of local
predisposing factors such as calculus, and adjustment of overhanging restorations.
Comprehensive oral hygiene instruction and motivation is provided at each visit as required.
This oral hygiene advice recommends tooth brushing and flossing after every meal and rinsing
with 0.12% non-alcohol based chlorhexidine mouth wash. These treatments are provided on 3
occasions at weekly intervals commencing at 20 weeks gestation.
Local anaesthesia is employed as required (1% lignocaine with 1:80,000 adrenalin up to a
maximum dose of 10mls).
Four weeks after the final treatment, at approximately 28 weeks gestation, a further visit is
made to re-evaluate periodontal status using clinical examination and the Florida probe. This
examination provides a quantifiable assessment of the success of treatment. Those women in
whom treatment has been unsuccessful are offered a further 3-visit treatment plan and we
estimate this will be required in 5-10% of the sample. A further two visits, each of 45
minutes duration is scheduled for 32 and 36 weeks gestation, at which times periodontal
supportive care and oral hygiene instruction and motivation are carried out as required.
Periodontal parameters at these visits are recorded.
Full infection control barrier techniques are employed and are stringent. Procedures include
gowns, disposable gloves and masks, eye protection for examiner and patient, and barrier
methods to avoid contamination.
Systemic antibiotic treatment is not employed except in cases in which there is evidence of
multiple periodontal abscesses, impaired immune response or poorly controlled diabetes. In
such cases treatment involves oral metronidazole and amoxycillin in standard doses for 5 days
commencing with the treatment. In the pilot study we observed no cases meeting these
criteria.
Control Group:
Women allocated to the control group are offered periodontal care after birth commencing 6
weeks after delivery. This care involves the same initial assessment and 3-visit treatment
protocol as for women in the treatment group. A further full periodontal examination is
conducted 4 weeks later.
After completion of their involvement in the study, women in both groups will be offered
ongoing maintenance care at OCHWA and this care will be free of charge if they hold a health
care card.
Women Who Deliver Pre-Term:
Those women who deliver pre-term will be offered a further screening examination at OHCWA and
treatment as for the control group. Information in this regard will be provided at the time
of recruitment.
Obstetric Management:
The obstetric and midwifery health care providers are unaware of the treatment allocation of
each woman in the study. Care is provided according to the standard protocols employed within
each hospital.
Sample Size:
The sample is enriched by advertising in the general media and in our peripheral public
hospitals for women with poor oral health or a history of pre-term birth to attend KEMH for a
single visit between 12 and 20 weeks gestation for periodontal examination.
A sample size of 540 women in each arm provides power to detect a reduction in the rate of
pre-term birth from 12% to 7% with power of 90% and an alpha level of 5%. Our pilot study of
272 women revealed a rate of periodontal disease of 15% in unselected women. With enrichment
by advertising for women at higher risk, we estimate the rate of periodontal disease will be
20%. Thus, for a total study size of 1080 women, 5400 need to be screened, which is rate of
45 each week in a 48 week working year. This sample size estimate allows two interim
analyses.
Statistical Considerations:
A data monitoring committee will be formed and will include an independent statistician who
will conduct the interim analysis. The committee will cease the trial if pre-determined rates
of benefit or harm are achieved. Analyses will be conducted on an intention-to-treat basis
using tests of proportions and logistic regression that allow for multiple adjustment for
covariates. Secondary analyses will be conducted of dose-response of treatment and
appropriate comparisons made with women who received periodontal examinations but did not
meet eligibility criteria. All hypothesis testing will be two sided and significance will be
at the 5% level.
