Rh IsoimmunizationPhase 3NCT00295516
Doppler or Amniocentesis to Predict Fetal Anemia
A Phase 3 study testing Fetal Middle Cerebral Artery Doppler measurement in people with Rh Isoimmunization, run by University of Toronto at 1 site in Canada.
Trial summary
In pregnancies complicated by Rhesus disease, the mother has developed antibodies which cross the placenta and can cause anemia and death of the fetus. When the anemia is detected on time, the fetus can be saved by giving it blood transfusions during the pregnancy. Read more about this study
- Who is it for?
- Ages 0 years and older
- Conditions the study is for
- Rh Isoimmunization
- What is being tested?
- Fetal Middle Cerebral Artery Doppler measurement
- Type of treatment
- Surgery or procedure
- How many people
- 157 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2000to Aug 2004
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Pregnant women with red cell alloimmunization associated with a risk of fetal anemia (D, E, c or Duffy (Fya )antibodies, alone or in combination with other antibodies)
- Gestational age between 12 and 34 weeks at study entry, viable fetus and accurate dating
- Maternal serum test-result, above the threshold at which the fetus is considered to be at risk of developing hemolytic anemia and thus a potential candidate for invasive testing.
Who cannot join
- Presence of Kell-antibodies
- Presence of fetal hydrops at first ultrasonographic examination
- Major fetal congenital or chromosomal anomalies
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Minimally Invasive Management of Rh Alloimmunization: Can Amniotic Fluid DeltaOD450 Measurements Be Replaced by Doppler Studies?
In pregnancies complicated by Rhesus disease, the mother has developed antibodies which cross the placenta and can cause anemia and death of the fetus. When the anemia is detected on time, the fetus can be saved by giving it blood transfusions during the pregnancy.
The standard test to predict whether the fetus needs a blood transfusion is examination of the amniotic fluid. To obtain this fluid a needle has to be inserted in the womb, which has a risk of preterm delivery, infection, and making the disease worse. This is called amniocentesis.
Read more
A new safe test, using Doppler ultrasound, has been developed to possibly replace the amniocentesis.
The aim of this study is to compare the new Doppler test with the standard amniocentesis. If the Doppler test is at least as good, this safe test may replace the amniocentesis in the management of pregnancies with Rhesus disease.
Read the detailed description
In pregnancies complicated by red cell alloimmunization, the fetus may suffer from chronic progressive hemolytic anemia. Severe fetal anemia leading to hydrops and fetal demise can occur as early as 17 weeks' gestation, while in other pregnancies the only manifestation of the disease is neonatal hyperbilirubinemia. The standard of care in the management of these pregnancies is to select patients at risk of fetal anemia using information about their obstetric history, and serial maternal serum antibody measurements. The selected patients are followed closely, usually in referral centers with a special interest and expertise in managing this now relatively rare disease. Ultrasound evaluation of fetal condition, with emphasis on signs of fetal hydrops, is performed regularly. In addition, serial amniocentesis is done to assess amniotic fluid bilirubin (deltaOD450) values. This spectrophotometric method estimates the level of bilirubin in the amniotic fluid, which correlates with the severity of the hemolytic process.
Although this diagnostic test, introduced by Liley in 1961, has served fetal medicine specialists well for almost 40 years, the invasive nature of the method is considered a serious disadvantage. Furthermore, its reliability has been questioned, especially when used in the second trimester. In the past decade, noninvasive alternative methods to predict the degree of fetal anemia have been developed.
The most promising of these new diagnostic tests is Doppler measurement of fetal blood flow velocities. Fetal blood flow velocity has been shown to correlate linearly with the degree of anemia. Recently, middle cerebral artery (MCA) peak flow velocity measurements have been reported to reliably predict presence or absence of fetal anemia.
The aim of this study is to compare the performance of this new noninvasive diagnostic test with the standard test, amniocentesis for amniotic fluid deltaOD450 values. In an international multicenter setting, a large cohort of consecutive Rh-alloimmunized pregnancies will be studied prospectively. Both diagnostic tests will be performed simultaneously in all patients, and compared with the "gold standard", fetal blood sampling (FBS) to assess the actual hemoglobin concentration.
- Conditions
- Rh Isoimmunization
- Being tested
- Fetal Middle Cerebral Artery Doppler measurement
- Keywords
- Rhesus, Isoimmunization, Red Cell Alloimmunization, Fetal Hemolytic Anemia, Erythroblastosis fetalis
- Medical subject headings
- Erythroblastosis, Fetal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fetal Middle Cerebral Artery Doppler measurementProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity Middle Cerebral Artery (MCA) peak velocity Doppler measurement and amniotic fluid deltaOD450 measurements, to predict fetal anemia requiring transfusion.
Specificity of Middle Cerebral Artery (MCA) peak velocity Doppler measurement and amniotic fluid deltaOD450 measurements, to predict fetal anemia requiring transfusion.
Secondary outcomes (1)
Comparison of the sensitivity and specificity of the original, linearly extended Liley chart with the Queenan (1993) chart, by plotting the deltaOD450 results found in our study in both charts.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2006 (estimated)
- Study startOct 2000
- Study completionAug 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rh IsoimmunizationStudies of the same condition, open and under way.
- More trials run by University of TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 157 participants
Sponsor and investigators
- Lead sponsor
- University of Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation, Stichting Oranjekliniek, The Netherlands
- Investigators
- Dick Oepkes, MD, PhD, Principal investigator, Leiden University Medical Centre, The NetherlandsGareth P Seaward, MB, BCh, MSc, Principal investigator, Mt.Sinai Hospital, University of Toronto, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00295516
- Sponsor's protocol ID
- MSH-REB 01-0266-U
- Other IDs
- PSI Grant Number:01-13
- Status last verified
- Feb 2006
- First submitted
- 22 Feb 2006
- Last updated
- 24 May 2006
- Results posted
- No
Publications
Oepkes D, Seaward PG, Vandenbussche FP, Windrim R, Kingdom J, Beyene J, Kanhai HH, Ohlsson A, Ryan G; DIAMOND Study Group. Doppler ultrasonography versus amniocentesis to predict fetal anemia. N Engl J Med. 2006 Jul 13;355(2):156-64. doi: 10.1056/NEJMoa052855.
PubMed 16837679
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Minimally Invasive Management of Rh Alloimmunization: Can Amniotic Fluid DeltaOD450 Measurements Be Replaced by Doppler Studies?
- ClinicalTrials.gov ID
- NCT00295516
- Acronym / sponsor ID
- MSH-REB 01-0266-U
- Conditions
- Rh Isoimmunization
- Keywords
- Rhesus, Isoimmunization, Red Cell Alloimmunization, Fetal Hemolytic Anemia, Erythroblastosis fetalis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 157 participants
- Lead sponsor
- University of TorontoUniversity, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation, Stichting Oranjekliniek, The Netherlands
- Study start
- Oct 2000
- Study completion
- Aug 2004
- First posted
- 23 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In pregnancies complicated by Rhesus disease, the mother has developed antibodies which cross the placenta and can cause anemia and death of the fetus. When the anemia is detected on time, the fetus can be saved by giving it blood transfusions during the pregnancy.
The standard test to predict whether the fetus needs a blood transfusion is examination of the amniotic fluid. To obtain this fluid a needle has to be inserted in the womb, which has a risk of preterm delivery, infection, and making the disease worse. This is called amniocentesis.
A new safe test, using Doppler ultrasound, has been developed to possibly replace the amniocentesis.
The aim of this study is to compare the new Doppler test with the standard amniocentesis. If the Doppler test is at least as good, this safe test may replace the amniocentesis in the management of pregnancies with Rhesus disease.
Detailed description
In pregnancies complicated by red cell alloimmunization, the fetus may suffer from chronic progressive hemolytic anemia. Severe fetal anemia leading to hydrops and fetal demise can occur as early as 17 weeks' gestation, while in other pregnancies the only manifestation of the disease is neonatal hyperbilirubinemia. The standard of care in the management of these pregnancies is to select patients at risk of fetal anemia using information about their obstetric history, and serial maternal serum antibody measurements. The selected patients are followed closely, usually in referral centers with a special interest and expertise in managing this now relatively rare disease. Ultrasound evaluation of fetal condition, with emphasis on signs of fetal hydrops, is performed regularly. In addition, serial amniocentesis is done to assess amniotic fluid bilirubin (deltaOD450) values. This spectrophotometric method estimates the level of bilirubin in the amniotic fluid, which correlates with the severity of the hemolytic process.
Although this diagnostic test, introduced by Liley in 1961, has served fetal medicine specialists well for almost 40 years, the invasive nature of the method is considered a serious disadvantage. Furthermore, its reliability has been questioned, especially when used in the second trimester. In the past decade, noninvasive alternative methods to predict the degree of fetal anemia have been developed.
The most promising of these new diagnostic tests is Doppler measurement of fetal blood flow velocities. Fetal blood flow velocity has been shown to correlate linearly with the degree of anemia. Recently, middle cerebral artery (MCA) peak flow velocity measurements have been reported to reliably predict presence or absence of fetal anemia.
The aim of this study is to compare the performance of this new noninvasive diagnostic test with the standard test, amniocentesis for amniotic fluid deltaOD450 values. In an international multicenter setting, a large cohort of consecutive Rh-alloimmunized pregnancies will be studied prospectively. Both diagnostic tests will be performed simultaneously in all patients, and compared with the "gold standard", fetal blood sampling (FBS) to assess the actual hemoglobin concentration.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 0 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Pregnant women with red cell alloimmunization associated with a risk of fetal anemia (D, E, c or Duffy (Fya )antibodies, alone or in combination with other antibodies)
- Gestational age between 12 and 34 weeks at study entry, viable fetus and accurate dating
- Maternal serum test-result, above the threshold at which the fetus is considered to be at risk of developing hemolytic anemia and thus a potential candidate for invasive testing.
Key exclusion criteria (3 listed)
- Presence of Kell-antibodies
- Presence of fetal hydrops at first ultrasonographic examination
- Major fetal congenital or chromosomal anomalies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fetal Middle Cerebral Artery Doppler measurement | Procedure or surgery | – |
Primary outcome
Sensitivity Middle Cerebral Artery (MCA) peak velocity Doppler measurement and amniotic fluid deltaOD450 measurements, to predict fetal anemia requiring transfusion.
Specificity of Middle Cerebral Artery (MCA) peak velocity Doppler measurement and amniotic fluid deltaOD450 measurements, to predict fetal anemia requiring transfusion.
1 secondary outcome
Comparison of the sensitivity and specificity of the original, linearly extended Liley chart with the Queenan (1993) chart, by plotting the deltaOD450 results found in our study in both charts.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2006.
- Derived from this study: PubMed 16837679Oepkes D, Seaward PG, Vandenbussche FP, Windrim R, Kingdom J, Beyene J, Kanhai HH, Ohlsson A, Ryan G; DIAMOND Study Group. Doppler ultrasonography versus amniocentesis to predict fetal anemia. N Engl J Med. 2006 Jul 13;355(2):156-64. doi: 10.1056/NEJMoa052855.
Related trials for Rh Isoimmunization
RecruitingPhase 2
Neonatal Outcomes on Direct Fetal Intravenous Immunoglobulin During Intrauterine Transfusion for Rhesus Isoimmunization
Hemolytic Disease of the Newborn, Fetal Anemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dick Oepkes, MD, PhD principal investigator
Leiden University Medical Centre, The Netherlands
Gareth P Seaward, MB, BCh, MSc principal investigator
Mt.Sinai Hospital, University of Toronto, Canada
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fetal Middle Cerebral Artery Doppler measurement in people with Rh Isoimmunization, run by University of Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity Middle Cerebral Artery (MCA) peak velocity Doppler measurement and amniotic fluid deltaOD450 measurements, to predict fetal anemia requiring transfusion.. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00295516, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2006.