Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000113459
Ethics application status
Not yet submitted
Date submitted
11/08/2006
Date registered
8/02/2007
Date last updated
8/02/2007
Type of registration
Retrospectively registered

Titles & IDs
Public title
A randomised phase III study to evaluate the effects of methotrexate in the treatment of women with an ectopic pregnancy to prevent the need for surgical intervention.
Scientific title
A randomised phase III study to evaluate the effects of methotrexate in the treatment of women with an ectopic pregnancy to prevent the need for surgical intervention.
Universal Trial Number (UTN)
Trial acronym
RCTEP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ectopic pregnancy 1605 0
Condition category
Condition code
Reproductive Health and Childbirth 1709 1709 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Method of Study
Day of Presentation
• Diagnosis of tubal ectopic pregnancy on TVS
• Serum hCG, full blood count (FBC), group and save (G&S), liver and renal function tests
• Providing patient fulfils above criteria, for possible inclusion in the study
• Information leaflets given and advised to return in 48 hours for repeat hCG

48 hours later
• If still asymptomatic and fulfilling the above criteria for possible participation in the study
• If patient agrees to participate in study, consent form to be signed
• Repeat hCG, FBC, liver and renal function tests to be taken.
• If the hCG has decreased over the 48 hours for randomisation to either expectant (‘wait and see’) management or medical management in the form of intramuscular methotrexate
• If the hCG has increased over the 48 hours for randomisation to either medical management in the form of methotrexate or surgery

Medical Management
• On this second visit intramuscular methotrexate will be given at a dose of 50mg/m2
• Repeat visits will then be required on days 3,4,5 and day 7 post methotrexate to measure the serum hCG. In addition on day 7 FBC, liver and renal function tests will be checked. (Day 1 = day of methotrexate)
• If the hCG decreases by more than 15 % between days 4 and 7, the hCG will then be checked on a weekly basis until less than 15 IU/L
• If it does not decrease by more than 15 % the woman will be rescanned and provided she is still asymptomatic and there are no changes on TVS, a second dose of methotrexate will be given. She will then be followed up with the same blood tests on days 3,4,5 and 7 post the second injection.
• Regardless of the hCG change, if at any point the woman becomes symptomatic of there are any changes on USS such as haemoperitoneum, fetal cardiac activity or an increase in the size of the ectopic mass, she will be assessed with regard to laparoscopy and subsequent surgical treatment.

Expectant Management
• Blood tests to measure hCG will continue to be repeated every 48 hours, as long as they are not increasing until the hCG decrease is more than 15%.
• Then blood tests will be repeated weekly until the levels are less than 15 IU/L
• If at any point the woman becomes symptomatic of the hCG is increasing she will be assessed to see whether or not she should receive methotrexate and be followed up as above, or should undergo surgery.

Surgical Management
• In the majority of cases surgery will be laparoscopic, but occasionally a laparotomy will be required
• If a laparoscopy is performed this will probably be done as a day case and therefore an over night stay avoided.
• Either a salpingectomy or salpingostomy will be performed depending on the findings at the time.
• Serial hCG follow up will be needed if a salpingostomy is performed or the ectopic pregnancy is ruptured. Levels will be taken weekly until less than 15 IU/l. If the levels plateau, methotrexate may need to be given.


Subsequent Follow Up
• Those treated surgically will be seen in clinic 2 weeks after the operation
• Those treated expectantly or medically will be seen at 3 months
Intervention code [1] 1303 0
Treatment: Other
Comparator / control treatment
No comparator.
Control group
Active

Outcomes
Primary outcome [1] 2380 0
The primary outcome measure is successful conservative (non-surgical) management of ectopic pregnancy. This is defined as successful resolution of the pregnancy measured by a decrease in serum hCG levels to less than 15 IU/L without the need for surgical intervention, whether after treatment with methotrexate or just expectant management.
Timepoint [1] 2380 0
Serum hCG measurements will be performed every week following implementation of the conservative management strategies. The weekly measurements will continue until the serum hCG levels are less than 15 IU/L; this could take as little as 14 days or as long as 65 days and depends on the starting serum hCG level.
Secondary outcome [1] 4130 0
• Time to resolution; i.e. when the serum hCG is less than 15 IU/L. This may take as many as 65 days depending on the starting serum hCG. Please refer to primary outcome field.
Timepoint [1] 4130 0
Secondary outcome [2] 4131 0
• Number of follow up visits – blood tests and ultrasound scan needed
Timepoint [2] 4131 0
Secondary outcome [3] 4132 0
• Need for second dose of methotrexate. This is determined at day 7; if the serum hCG fall is less than 15% between days 4 and 7, then a repeat dose of methotrexate is given.
Timepoint [3] 4132 0
Secondary outcome [4] 4133 0
• Need for methotrexate in those initially managed expectantly. This would be the case if the serum hCG levels began to rise in a woman whose hCG levels were noted initially to fall at 48 hours.
Timepoint [4] 4133 0
Secondary outcome [5] 4134 0
• Reasons for surgical intervention. Signs of tubal rupture can occur at any time during the treatment and even in the presence of falling serum hCG levels. Under these circumstances, i.e. worsening lower abdominal pain, clinical instability or signs of blood in the pelvis on ultrasound scan, surgical intervention would be instigated.
Timepoint [5] 4134 0
Secondary outcome [6] 4135 0
• Subsequent reproductive outcome.
Timepoint [6] 4135 0
This will be measured in the first twelve months after the treatment has been completed.

Eligibility
Key inclusion criteria
Pre-menopausal women • Asymptomatic• Haemodynamically stable• Serum human chorionic gonadotrophin level (hCG) less than 3000 IU/L• No haemoperitoneum• Absence of fetal cardiac activity on TVS• No contraindication to the use of methotrexate• Normal liver and renal function.
Minimum age
18 Years
Maximum age
Not stated
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
• In pain• Haemodynamically unstable• Serum hCG > 3000 IU/L• Haemoperitoneum on TVS• Fetal cardiac activity on TVS• Co-existing intrauterine pregnancy• Contraindication to the use of methotrexate• Abnormal liver or kidney function• Unable to attend for follow up clinic visits• Learning difficulties, patients under the age of 18 and other vulnerable groups, e.g. mental illness, dementia due to issues regarding informed consent.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by phone/fax /computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomization table created by a computer software (i.e., computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/01/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 1854 0
Hospital
Name [1] 1854 0
Early Pregnancy Unit, Nepean Clinical School, University of Sydney, Nepean Hospital
Country [1] 1854 0
Australia
Primary sponsor type
Individual
Name
Associate Professor George Condous
Address
c/o Early Pregnancy Unit
Nepean Clinical School
University of Sydney
Nepean Hospital
Penrith NSW
Country
Secondary sponsor category [1] 1669 0
None
Name [1] 1669 0
Nil
Address [1] 1669 0
Country [1] 1669 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 3461 0
Nepean Hospital
Ethics committee address [1] 3461 0
Ethics committee country [1] 3461 0
Australia
Date submitted for ethics approval [1] 3461 0
Approval date [1] 3461 0
11/08/2006
Ethics approval number [1] 3461 0

Summary
Brief summary
Hypothesis

The null hypotheses are:

1. In women with an hCG ratio < 0.8 (fall in serum hCG over 48 h of more than 20%) there is no difference in success of conservative management whether managed expectantly or medically with methotrexate.
2. In women with an hCG ratio > 0.8 surgery is needed whether or not methotrexate is given as first line management.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27753 0
Address 27753 0
Country 27753 0
Phone 27753 0
Fax 27753 0
Email 27753 0
Contact person for public queries
Name 10492 0
George Condous
Address 10492 0
Associate Professor
Early Pregnancy Unit
Nepean Clinical School
Level 5 South Block
University of Sydney
Nepean Hospital
Penrith
NSW 2750
Sydney
Country 10492 0
Australia
Phone 10492 0
(02) 47341474
Fax 10492 0
(02) 47341817
Email 10492 0
[email protected]
Contact person for scientific queries
Name 1420 0
George Condous
Address 1420 0
Senior Lecturer
Early Pregnancy Unit
Nepean Clinical School
Level 5 South Block
University of Sydney
Nepean Hospital
Penrith
NSW 2750
Sydney
Country 1420 0
Australia
Phone 1420 0
(02) 47341474
Fax 1420 0
(02) 47341817
Email 1420 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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