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Trial registered on ANZCTR


Registration number
ACTRN12617000226303
Ethics application status
Approved
Date submitted
6/10/2016
Date registered
13/02/2017
Date last updated
18/04/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Treating preterm preeclampsia with sulfasalazine: An early phase clinical trial
Scientific title
Pharmacokinetics of sulfasalazine for the treatment of preterm preeclampsia: An early phase clinical trial
Secondary ID [1] 290280 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Preeclampsia 300516 0
Condition category
Condition code
Reproductive Health and Childbirth 300378 300378 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
3 grams of sulfasalazine will be administered orally daily to participants until they require delivery. Patients will be admitted and adherence monitored using the in patient drug chart.
Intervention code [1] 296082 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 299830 0
1) Our primary outcome is to assess the pharmacokinetic profile of sulfasalazine in patients with preeclampsia. Pharmacokinetic parameters include maximum concentration (Cmax) and time to maximum concentration (Tmax), area under the concentration time curve (AUC), apparent oral clearance (CL/F), half life and renal clearance.

2) These will be assessed in maternal blood and urine over a 24 hour period. We will also assess sulfasalazine levels in maternal blood, cord blood and placenta at delivery.
Timepoint [1] 299830 0
* Serial blood samples of 6 mls will be collected over one 24 hour period, after at least 24 hours of sulfasalazine treatment, to assess levels of sulfasalazine levels at 0, 2, 4, 8, 12 and 24 hours.
* Urine will be collected before the dose, and then at 0-4, 4-8, 8-12 and 12-24 hours and sulfasalazine excretion assessed.
* Maternal, umbilical cord and placenta will be collected at time of delivery to assess sulfasalazine and sulfapyridine levels.
Secondary outcome [1] 328228 0
To determine the effects of sulfasalazine on clinical markers of preeclampsia including:
Headache. This will be assessed by asking the patient daily whether they have a headache.
Timepoint [1] 328228 0
This will be examined daily antenatally and postnatally until patient discharge.
Secondary outcome [2] 330644 0
Biochemical markers of preeclampsia including full blood count in particular haemoglobin and platelet count, electrolytes: including creatinine, urea and uric acid and coagulation profile using a serum blood sample.
Timepoint [2] 330644 0
These will be examined daily antenatally and postnatally until patient discharge.
Secondary outcome [3] 330645 0
In the fetus/neonate we will assess mortality
Timepoint [3] 330645 0
This will be obtained by accessing the patient records.
Secondary outcome [4] 331348 0
Visual symptoms. This will be assessed by asking the patient daily whether they have spots in their vision or any visual disturbance.

Timepoint [4] 331348 0
This will be assessed daily until patient discharge.
Secondary outcome [5] 331349 0
Right upper quadrant abdominal pain. This will be assessed by asking the patient daily whether they have abdominal pain.

Timepoint [5] 331349 0
This will be assessed daily until discharge
Secondary outcome [6] 331350 0
Severe hypertension (blood pressure of systolic greater than or equal to 160 and diastolic greater than or equal to 110).
Timepoint [6] 331350 0
This will be assessed daily until discharge
Secondary outcome [7] 331351 0
Electrolytes: including creatinine, urea and uric acid using a serum blood sample.
Timepoint [7] 331351 0
This will be examined daily until delivery
Secondary outcome [8] 331352 0
coagulation profile in patient serum.
Timepoint [8] 331352 0
This will be assessed as decided by the treating clinician
Secondary outcome [9] 331353 0
proteinuria
Timepoint [9] 331353 0
This will be assessed daily until delivery.
Secondary outcome [10] 331354 0
In the neonate neurological morbidity including intraventricular haemorrhage diagnosed with clinical examination and ultrasound.
Timepoint [10] 331354 0
This outcome will be assessed by paediatricians daily after delivery to the date of discharge of the neonate.
Secondary outcome [11] 331355 0
In the neonate respiratory morbidity including respiratory distress syndrome will be assessed clinically by paediatricians and with x-ray if clinically indicated.
Timepoint [11] 331355 0
This outcome will be assessed by paediatricians daily after delivery to the date of discharge of the neonate.
Secondary outcome [12] 331356 0
In the neonate retinopathy of prematurity will be assessed clinically by the paediatrician.
Timepoint [12] 331356 0
This outcome will be assessed daily by paediatricians after delivery to the date of discharge of the neonate.
Secondary outcome [13] 331357 0
In the neonate gastrointestinal morbidity including necrotising enterocolitis will be assessed clinically by the paediatrician.
Timepoint [13] 331357 0
This outcome will be assessed by paediatricians daily after delivery to the date of discharge of the neonate.

Eligibility
Key inclusion criteria
The diagnosis of preeclampsia will be made using the Society of Obstetric Medicine Australia and New Zealand guidelines. Eligible women will be 18 years or older with singleton, non-anomalous pregnancies between 30+0 and 36+0 weeks gestation.
Minimum age
18 Years
Maximum age
45 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
We will exclude women with multiple pregnancy, known fetal malformation, contraindication to sulfasalazine treatment, women already taking sulfasalazine and women with an immunodeficiency disorder.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 6780 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [2] 6781 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 14435 0
3084 - Heidelberg
Recruitment postcode(s) [2] 14436 0
3021 - St Albans

Funding & Sponsors
Funding source category [1] 294653 0
Charities/Societies/Foundations
Name [1] 294653 0
Norman Beischer Medical Research Foundation
Address [1] 294653 0
Mercy Hospital for Women
163 Studley Road
Heidelberg
Victoria
3084
Country [1] 294653 0
Australia
Primary sponsor type
Hospital
Name
Mercy Hospital for Women
Address
Mercy Hospital for Women
163 Studley Road
Heidelberg
Victoria
3084
Country
Australia
Secondary sponsor category [1] 293513 0
None
Name [1] 293513 0
NA
Address [1] 293513 0
NA
Country [1] 293513 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296092 0
Mercy Human Research Ethics Committee
Ethics committee address [1] 296092 0
Mercy Hospital for Women
163 Studley Road
Heidelberg
Victoria
3084
Ethics committee country [1] 296092 0
Australia
Date submitted for ethics approval [1] 296092 0
10/10/2016
Approval date [1] 296092 0
12/01/2017
Ethics approval number [1] 296092 0
R16/65

Summary
Brief summary
Preeclampsia is a common, serious complication of pregnancy and leading cause of maternal, fetal and neonatal death and disability. Currently there is no medical treatment and the only way to stop disease progression is to deliver the pregnancy. At early gestations this inflicts the serious risks of prematurity on the newborn whilst the mother is exposed to the risk of disease progression during the delivery process. A treatment that stabilises the disease to allow the safe prolongation of pregnancy would be a major advance.

Excitingly we have discovered that a medication safe in pregnancy, sulfasalazine, can reverse key features of preeclampsia disease pathophysiology in laboratory studies using primary human pregnancy tissues. Firstly we showed that sulfasalazine reduces the placental secretion of antiangiogenic factors sFlt-1 and soluble endoglin that cause preeclampsia. Secondly we demonstrated sulfasalazine reduced features of vascular dysfunction specific to preeclampsia.

Given these promising findings and that sulfasalazine is safe in pregnancy (category B) we hope to progress this concept and translate these findings from the laboratory to the clinic with a proof of concept early phase clinical trial. We propose to recruit 20 women with preterm preeclampsia (30+0 weeks to 36+0 weeks gestation) at The Mercy Hospital for Women and treat them with 2-3 grams of sulfasalazine per day. We will assess the pharmacokinetics of sulfasalazine in women with preeclampsia and monitor key clinical and biochemical features of the disease.

If successful, at the completion of this study, we will have evidence to progress the study of sulfasalazine as a treatment for preeclampsia to randomized clinical trial. It may form the basis for a medical treatment for preeclampsia and reduce the devastating burden of this common obstetric disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69502 0
Dr Fiona Brownfoot
Address 69502 0
Mercy Hospital for Women
163 Studley Road
Heidelberg
Victoria
3084
Country 69502 0
Australia
Phone 69502 0
+61 3 8458 4000
Fax 69502 0
Email 69502 0
fiona.brownfoot@unimelb.edu.au
Contact person for public queries
Name 69503 0
Dr Fiona Brownfoot
Address 69503 0
Mercy Hospital for Women
163 Studley Road
Heidelberg
Victoria
3084
Country 69503 0
Australia
Phone 69503 0
+61 3 8458 4000
Fax 69503 0
Email 69503 0
fiona.brownfoot@unimelb.edu.au
Contact person for scientific queries
Name 69504 0
Dr Fiona Brownfoot
Address 69504 0
Mercy Hospital for Women
163 Studley Road
Heidelberg
Victoria
3084
Country 69504 0
Australia
Phone 69504 0
+61 3 8458 4000
Fax 69504 0
Email 69504 0
fiona.brownfoot@unimelb.edu.au

No information has been provided regarding IPD availability
Summary results
No Results