Rhesus Negative Pregnant WomenGENIFERHNCT00832962
Routine Fetal RhD Genotyping for RhD- Pregnant Women
An observational study of Rhesus Negative Pregnant Women, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The study is divided in two sub-studies. The first one is an economical and performance comparison between two antenatal management strategies of RhD negative pregnant women: the first one will comprise non invasive RhD fetal typing during the second trimester of pregnancy (GENIFERH 1 RhD typing group), and the second… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Rhesus Negative Pregnant Women
- What is being tested?
- Genotyping and Usual prophylaxis
- How many people
- 2,532 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2009to Oct 2013
- Phase
- Observational
- 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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Adult Rh negative pregnant women followed in the participating centers
Who may be able to join
- Adult Rh negative pregnant patients ( ≥ 18 years)
- Valid and confirmed result of Rh D negative status.(one copy saved into the obstetrical records)
- Absence of actively produced anti-D antibody as shown on laboratory examination of a blood sample taken within the first trimester of pregnancy.
- Evolving pregnancy at the time of inclusion in the study ( between 8 and 26 gestation weeks as confirmed by early sonography).
- Absence of a previous invasive fetal RHD genotyping ( chorionic villous sampling, amniocentesis).
- Patient having signed an informed consent for the study.
- Inclusion and delivery expected in the same maternity ward
- Patient affiliated to a social security regimen.
Who cannot join
- Evolving pregnancy seen for the first time after 26 gestation weeks.
- Poor understanding of the objectives of the study ( language barrier, ...)
- Delivery expected in a maternity ward not participating at the study.
- Fetal RHD invasive genotyping performed during early pregnancy on amniotic fluid or chorionic villus.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effectiveness of Routine Fetal RhD Genotyping for RhD- Pregnant Women
The study is divided in two sub-studies. The first one is an economical and performance comparison between two antenatal management strategies of RhD negative pregnant women: the first one will comprise non invasive RhD fetal typing during the second trimester of pregnancy (GENIFERH 1 RhD typing group), and the second will be a conventional management, i.e. without RHD fetal typing (GENIFERH 1 control group). The two groups will consist of 13 maternity wards spread over French territory. The second study (GENIFERH 2) is an evaluation of RhD fetal typing diagnostic performance and biological feasibility in routine antenatal practice with development of knew technical support; it will be based on more than 3500 fetal genotypings performed during one year by the five laboratories participating at the two studies.
Read the detailed description
Alloimmunisation against the RhD (RH) red cell surface antigen is the commonest cause of haemolytic disease of the fetus and newborn. It can be avoided by anti D immunoglobulin administration (RhIg). At the end of year 2005, new recommendations about anti-D prophylaxis in France proposed that all RhD negative pregnant women should be given anti-D immunoglobulin at 28 weeks' gestation. However, about one third of these women would be carrying an RhD negative fetus and would receive the treatment unnecessarily. A non-invasive fetal RHD typing kit, CE labelled since June 2007, is available and could be proposed to all RhD negative pregnant women. Applicable from the end of the first trimester of pregnancy on fetal DNA isolated from maternal plasma, this assay allows RhIg to be specifically injected to unsensitized pregnancies with RhD positive fetus only, and to promote the use of antenatal RhIg prophylaxis in a rational approach with economical and ethical impact.The study is divided in two sub-studies. The first one is an economical and performance comparison between two antenatal management strategies of RhD negative pregnant women: the first one will comprise non invasive RhD fetal typing during the second trimester of pregnancy (GENIFERH 1 RhD typing group), and the second will be a conventional management, i.e. without RHD fetal typing (GENIFERH 1 control group). The two groups will consist of 13 maternity wards spread over French territory. The second study (GENIFERH 2) is an evaluation of RhD fetal typing diagnostic performance and biological feasibility in routine antenatal practice with development of knew technical support; it will be based on more than 3500 fetal genotypings performed during one year by the five laboratories participating at the two studies.
- Conditions
- Rhesus Negative Pregnant Women
- Being tested
- Genotyping, Usual prophylaxis
- Keywords
- Rhesus D, Anti-D allo-immunization, Fetal RHD genotyping, anti-D immunoglobulins, anti-D prophylaxis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GenotypingGenetic
Whole blood sample
Usual prophylaxisOther
Also called Prophylactic anti-RhD
Prophylactic anti-RhD
| Study group | Role | What they receive |
|---|---|---|
| 1 | Adult Rh negative pregnant patients from 7 selected centers (SAINT ANTOINE hospital, CHU Marseille, CHU Nantes, CHU Lille, LOUIS MOURIER Hospital, SAINT VINCENT-PAUL Hospital, CH POISSY) Receives: Genetic: Genotyping | |
| 2 | Adult Rh negative pregnant patients from 6 selected centers (Tenon hospital, Jean VERDIER Hospital, La Pitie-Salpetriere Hospital, Cochin Hospital, Robert Debre Hospital, BICHAT Hospital) Receives: Other: Usual prophylaxis |
What is being measured
The primary outcome is the main question the study is designed to answer.
cost-effectiveness of the two strategies of antenatal management by comparing the rate of RhD negative women eligible for receiving RHIG that would have not receive prophylactic anti-RhD in the two populations, the one with fetal RHD typing and the other
Measured: At the end of the study
Secondary outcomes (4)
Assessment of the applicability of non invasive fetal RHD typing in the antenatal management of unimmunized Rh-negative pregnant patients in different settings.
Measured: At the end of the study
performance assessment of high throughput fetal RHD genotyping in hospital laboratories.
Measured: At the end of the study
Evaluation of the technical support needed to realize high throughput fetal RHD genotyping by authorized laboratories.
Measured: At the end of the study
Development and diffusion of external quality controls for non invasive fetal RHD genotyping.
Measured: At the end of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Rhesus Negative Pregnant WomenStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 2,532 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yves BROSSARD, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00832962
- Sponsor's protocol ID
- P 060410
- Other IDs
- IC 0606
- Acronym
- GENIFERH
- Status last verified
- Mar 2015
- First submitted
- 13 Jan 2009
- Last updated
- 26 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Branger B, Winer N. [Epidemiology of anti-D allo-immunization during pregnancy]. J Gynecol Obstet Biol Reprod (Paris). 2006 Feb;35(1 Suppl):1S87-1S92. French.
PubMed 16495833Parant O. [Comparison of the efficacy of different methods for the prevention of anti-D allo-immunization during pregnancy: targeted strategy limited to risk situations or associated with systematic prevention in the 3rd trimester]. J Gynecol Obstet Biol Reprod (Paris). 2006 Feb;35(1 Suppl):1S93-1S103. French.
PubMed 16495834Bennett PR, Le Van Kim C, Colin Y, Warwick RM, Cherif-Zahar B, Fisk NM, Cartron JP. Prenatal determination of fetal RhD type by DNA amplification. N Engl J Med. 1993 Aug 26;329(9):607-10. doi: 10.1056/NEJM199308263290903.
PubMed 8341334Aubin JT, Le Van Kim C, Mouro I, Colin Y, Bignozzi C, Brossard Y, Cartron JP. Specificity and sensitivity of RHD genotyping methods by PCR-based DNA amplification. Br J Haematol. 1997 Aug;98(2):356-64. doi: 10.1046/j.1365-2141.1997.2193040.x.
PubMed 9266934Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997 Aug 16;350(9076):485-7. doi: 10.1016/S0140-6736(97)02174-0.
PubMed 9274585Lo YM, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM, Wainscoat JS, Johnson PJ, Chang AM, Hjelm NM. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet. 1998 Apr;62(4):768-75. doi: 10.1086/301800.
PubMed 9529358Brossard Y, Sender A, Cartron JP, Huchet J, Pinon F, Blot P, David G. [Value of RHD fetal genotyping in the prevention of anti-D immunization]. Bull Acad Natl Med. 2001;185(2):329-36. French.
PubMed 11474588Faas BH, Beuling EA, Christiaens GC, von dem Borne AE, van der Schoot CE. Detection of fetal RHD-specific sequences in maternal plasma. Lancet. 1998 Oct 10;352(9135):1196. doi: 10.1016/s0140-6736(05)60534-x. No abstract available.
PubMed 9777844Rouillac-Le Sciellour C, Puillandre P, Gillot R, Baulard C, Metral S, Le Van Kim C, Cartron JP, Colin Y, Brossard Y. Large-scale pre-diagnosis study of fetal RHD genotyping by PCR on plasma DNA from RhD-negative pregnant women. Mol Diagn. 2004;8(1):23-31. doi: 10.1007/BF03260044.
PubMed 15230639Colin Y, Cherif-Zahar B, Le Van Kim C, Raynal V, Van Huffel V, Cartron JP. Genetic basis of the RhD-positive and RhD-negative blood group polymorphism as determined by Southern analysis. Blood. 1991 Nov 15;78(10):2747-52.
PubMed 1824267Singleton BK, Green CA, Avent ND, Martin PG, Smart E, Daka A, Narter-Olaga EG, Hawthorne LM, Daniels G. The presence of an RHD pseudogene containing a 37 base pair duplication and a nonsense mutation in africans with the Rh D-negative blood group phenotype. Blood. 2000 Jan 1;95(1):12-8.
PubMed 10607679Geifman-Holtzman O, Grotegut CA, Gaughan JP. Diagnostic accuracy of noninvasive fetal Rh genotyping from maternal blood--a meta-analysis. Am J Obstet Gynecol. 2006 Oct;195(4):1163-73. doi: 10.1016/j.ajog.2006.07.033.
PubMed 17000250Lo YM, Hjelm NM, Fidler C, Sargent IL, Murphy MF, Chamberlain PF, Poon PM, Redman CW, Wainscoat JS. Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma. N Engl J Med. 1998 Dec 10;339(24):1734-8. doi: 10.1056/NEJM199812103392402.
PubMed 9845707Finning K, Martin P, Daniels G. A clinical service in the UK to predict fetal Rh (Rhesus) D blood group using free fetal DNA in maternal plasma. Ann N Y Acad Sci. 2004 Jun;1022:119-23. doi: 10.1196/annals.1318.019.
PubMed 15251949van der Schoot CE. Molecular diagnostics in immunohaematology. Vox Sang. 2004 Jul;87 Suppl 2:189-92. doi: 10.1111/j.1741-6892.2004.00481.x. No abstract available.
PubMed 15209914
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of Routine Fetal RhD Genotyping for RhD- Pregnant Women
- ClinicalTrials.gov ID
- NCT00832962
- Acronym / sponsor ID
- GENIFERH / P 060410
- Conditions
- Rhesus Negative Pregnant Women
- Keywords
- Rhesus D, Anti-D allo-immunization, Fetal RHD genotyping, anti-D immunoglobulins, anti-D prophylaxis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,532 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 30 Jan 2009 (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.
The study is divided in two sub-studies. The first one is an economical and performance comparison between two antenatal management strategies of RhD negative pregnant women: the first one will comprise non invasive RhD fetal typing during the second trimester of pregnancy (GENIFERH 1 RhD typing group), and the second will be a conventional management, i.e. without RHD fetal typing (GENIFERH 1 control group). The two groups will consist of 13 maternity wards spread over French territory. The second study (GENIFERH 2) is an evaluation of RhD fetal typing diagnostic performance and biological feasibility in routine antenatal practice with development of knew technical support; it will be based on more than 3500 fetal genotypings performed during one year by the five laboratories participating at the two studies.
Detailed description
Alloimmunisation against the RhD (RH) red cell surface antigen is the commonest cause of haemolytic disease of the fetus and newborn. It can be avoided by anti D immunoglobulin administration (RhIg). At the end of year 2005, new recommendations about anti-D prophylaxis in France proposed that all RhD negative pregnant women should be given anti-D immunoglobulin at 28 weeks' gestation. However, about one third of these women would be carrying an RhD negative fetus and would receive the treatment unnecessarily. A non-invasive fetal RHD typing kit, CE labelled since June 2007, is available and could be proposed to all RhD negative pregnant women. Applicable from the end of the first trimester of pregnancy on fetal DNA isolated from maternal plasma, this assay allows RhIg to be specifically injected to unsensitized pregnancies with RhD positive fetus only, and to promote the use of antenatal RhIg prophylaxis in a rational approach with economical and ethical impact.The study is divided in two sub-studies. The first one is an economical and performance comparison between two antenatal management strategies of RhD negative pregnant women: the first one will comprise non invasive RhD fetal typing during the second trimester of pregnancy (GENIFERH 1 RhD typing group), and the second will be a conventional management, i.e. without RHD fetal typing (GENIFERH 1 control group). The two groups will consist of 13 maternity wards spread over French territory. The second study (GENIFERH 2) is an evaluation of RhD fetal typing diagnostic performance and biological feasibility in routine antenatal practice with development of knew technical support; it will be based on more than 3500 fetal genotypings performed during one year by the five laboratories participating at the two studies.
Study design
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Genetic: GenotypingAdult Rh negative pregnant patients from 7 selected centers (SAINT ANTOINE hospital, CHU Marseille, CHU Nantes, CHU Lille, LOUIS MOURIER Hospital, SAINT VINCENT-PAUL Hospital, CH POISSY) |
| 2 | – | Other: Usual prophylaxisAdult Rh negative pregnant patients from 6 selected centers (Tenon hospital, Jean VERDIER Hospital, La Pitie-Salpetriere Hospital, Cochin Hospital, Robert Debre Hospital, BICHAT Hospital) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult Rh negative pregnant women followed in the participating centers
Key inclusion criteria (8 listed)
- Adult Rh negative pregnant patients ( ≥ 18 years)
- Valid and confirmed result of Rh D negative status.(one copy saved into the obstetrical records)
- Absence of actively produced anti-D antibody as shown on laboratory examination of a blood sample taken within the first trimester of pregnancy.
- Evolving pregnancy at the time of inclusion in the study ( between 8 and 26 gestation weeks as confirmed by early sonography).
- Absence of a previous invasive fetal RHD genotyping ( chorionic villous sampling, amniocentesis).
Key exclusion criteria (4 listed)
- Evolving pregnancy seen for the first time after 26 gestation weeks.
- Poor understanding of the objectives of the study ( language barrier, ...)
- Delivery expected in a maternity ward not participating at the study.
- Fetal RHD invasive genotyping performed during early pregnancy on amniotic fluid or chorionic villus.
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 |
|---|---|---|
| GenotypingWhole blood sample | Genetic | 1 |
| Usual prophylaxisAlso: Prophylactic anti-RhDProphylactic anti-RhD | Other | 2 |
Primary outcome
cost-effectiveness of the two strategies of antenatal management by comparing the rate of RhD negative women eligible for receiving RHIG that would have not receive prophylactic anti-RhD in the two populations, the one with fetal RHD typing and the other
Time frame: At the end of the study
4 secondary outcomes
Assessment of the applicability of non invasive fetal RHD typing in the antenatal management of unimmunized Rh-negative pregnant patients in different settings.
Time frame: At the end of the study
performance assessment of high throughput fetal RHD genotyping in hospital laboratories.
Time frame: At the end of the study
Evaluation of the technical support needed to realize high throughput fetal RHD genotyping by authorized laboratories.
Time frame: At the end of the study
Development and diffusion of external quality controls for non invasive fetal RHD genotyping.
Time frame: At the end of the study
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 26 Mar 2015.
- Background: PubMed 16495833Branger B, Winer N. [Epidemiology of anti-D allo-immunization during pregnancy]. J Gynecol Obstet Biol Reprod (Paris). 2006 Feb;35(1 Suppl):1S87-1S92. French.
- Background: PubMed 16495834Parant O. [Comparison of the efficacy of different methods for the prevention of anti-D allo-immunization during pregnancy: targeted strategy limited to risk situations or associated with systematic prevention in the 3rd trimester]. J Gynecol Obstet Biol Reprod (Paris). 2006 Feb;35(1 Suppl):1S93-1S103. French.
- Background: PubMed 8341334Bennett PR, Le Van Kim C, Colin Y, Warwick RM, Cherif-Zahar B, Fisk NM, Cartron JP. Prenatal determination of fetal RhD type by DNA amplification. N Engl J Med. 1993 Aug 26;329(9):607-10. doi: 10.1056/NEJM199308263290903.
- Background: PubMed 9266934Aubin JT, Le Van Kim C, Mouro I, Colin Y, Bignozzi C, Brossard Y, Cartron JP. Specificity and sensitivity of RHD genotyping methods by PCR-based DNA amplification. Br J Haematol. 1997 Aug;98(2):356-64. doi: 10.1046/j.1365-2141.1997.2193040.x.
- Background: PubMed 9274585Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997 Aug 16;350(9076):485-7. doi: 10.1016/S0140-6736(97)02174-0.
- Background: PubMed 9529358Lo YM, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM, Wainscoat JS, Johnson PJ, Chang AM, Hjelm NM. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet. 1998 Apr;62(4):768-75. doi: 10.1086/301800.
- Background: PubMed 11474588Brossard Y, Sender A, Cartron JP, Huchet J, Pinon F, Blot P, David G. [Value of RHD fetal genotyping in the prevention of anti-D immunization]. Bull Acad Natl Med. 2001;185(2):329-36. French.
- Background: PubMed 9777844Faas BH, Beuling EA, Christiaens GC, von dem Borne AE, van der Schoot CE. Detection of fetal RHD-specific sequences in maternal plasma. Lancet. 1998 Oct 10;352(9135):1196. doi: 10.1016/s0140-6736(05)60534-x. No abstract available.
- Background: PubMed 15230639Rouillac-Le Sciellour C, Puillandre P, Gillot R, Baulard C, Metral S, Le Van Kim C, Cartron JP, Colin Y, Brossard Y. Large-scale pre-diagnosis study of fetal RHD genotyping by PCR on plasma DNA from RhD-negative pregnant women. Mol Diagn. 2004;8(1):23-31. doi: 10.1007/BF03260044.
- Background: PubMed 1824267Colin Y, Cherif-Zahar B, Le Van Kim C, Raynal V, Van Huffel V, Cartron JP. Genetic basis of the RhD-positive and RhD-negative blood group polymorphism as determined by Southern analysis. Blood. 1991 Nov 15;78(10):2747-52.
- Background: PubMed 10607679Singleton BK, Green CA, Avent ND, Martin PG, Smart E, Daka A, Narter-Olaga EG, Hawthorne LM, Daniels G. The presence of an RHD pseudogene containing a 37 base pair duplication and a nonsense mutation in africans with the Rh D-negative blood group phenotype. Blood. 2000 Jan 1;95(1):12-8.
- Background: PubMed 17000250Geifman-Holtzman O, Grotegut CA, Gaughan JP. Diagnostic accuracy of noninvasive fetal Rh genotyping from maternal blood--a meta-analysis. Am J Obstet Gynecol. 2006 Oct;195(4):1163-73. doi: 10.1016/j.ajog.2006.07.033.
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.
Yves BROSSARD, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rhesus Negative Pregnant Women, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 8 inclusion and 4 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 26 Mar 2015. 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 France. 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.
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?
cost-effectiveness of the two strategies of antenatal management by comparing the rate of RhD negative women eligible for receiving RHIG that would have not receive prophylactic anti-RhD in the two populations, the one with fetal RHD typing and the other (time frame: At the end of the study). 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 NCT00832962, which also lists 21 linked publications.
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 26 Mar 2015; AzTrials last refreshed its copy on 7 Nov 2026.