Cytomegalovirus DiseaseTT-CMVNCT00907686
TT-CMV Observational Birth Cohort Study
An observational study of Cytomegalovirus Disease, run by Emory University at 3 sites in United States.
Trial summary
The spread of viruses through transfusions is the cause of serious illness and death in recipients whose immune systems are unable to fight infection. Another group of patients whose immune systems are underdeveloped and can be affected by a particular virus known as cytomegalovirus (CMV) is low birthweight infants… Read more about this study
- Who is it for?
- Ages 1 hour to 5 days
- Conditions the study is for
- Cytomegalovirus Disease
- How many people
- 600 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2010to Apr 2014
- 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 1 hour to 5 days
- All sexes
- No healthy volunteers
- Child
Study population: Low birthweight infants in NICU.
Who may be able to join
- All LBWIs whose weight is ≤ 1500 grams at birth
- LBWI is within first five days of life
Who cannot join
- LBWI not expected to live past first seven days of life
- LBWI has a severe congenital abnormality
- LBWI has received a RBC or platelet transfusion at another institution prior to transfer
- LBWI has received an in-utero transfusion
- LBWI is clinically suspected of having toxoplasmosis, rubella, herpes infection(s) at birth
- Refusal by the mother to grant consent for herself and/or refusal to grant consent for her LBWI
- If the mother of the child has previously participated in this study
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Grady Memorial Hospital
Atlanta, Georgia, 30303
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Northside Hospital
Atlanta, Georgia, 30328
About this study
Official title: Prevention of Transfusion-transmitted CMV (TT-CMV) in Lowbirth Weight Infants (LBWI; ≤1500 Grams) Using CMV Seronegative and Leukoreduced Transfusions.
The spread of viruses through transfusions is the cause of serious illness and death in recipients whose immune systems are unable to fight infection. Another group of patients whose immune systems are underdeveloped and can be affected by a particular virus known as cytomegalovirus (CMV) is low birthweight infants (LBWIs). CMV can be spread through the placenta, during the birth process, through breast milk, while in the hospital or while caring for someone carrying the virus as well as through a transfusion, known as transfusion-transmitted (TT-CMV).
The spread of TT-CMV in LBWIs can be curtailed by transfusing blood products that are CMV negative as well as to filter the white cells in blood that carry the virus (leukoreduction). The purpose of this study is to see if the use of these two strategies can lower the spread of CMV through a transfusion. How "safe" the blood actually is through leukoreduction is not known and CMV still occurs in LBWIs. It is not clear whether this approach is optimal or whether additional safety steps are needed to completely prevent TT-CMV. Specific actions that could tell us when virus has reached the blood product or breast milk is to test each of these to determine if virus slipped "unnoticed" and/or when the product was not thoroughly filtered.
In this study, the investigators believe that the use of both prevention strategies will result in a lower rate of TT-CMV, and that the "cause" of TT-CMV may be found in the presence of CMV at the DNA level or by unfiltered white cells that remain in the blood product. Thus, the most significant clinical question that remains to be addressed is whether this double strategy for transfusion safety actually provides a "zero CMV-risk" blood supply or whether further safety measures (DNA testing + 100% leukoreduction) must be used to protect this extremely vulnerable patient group from CMV infection. This birth cohort study will be done with 6 participating NICUs, and will study both CMV positive and negative mothers in order to estimate the rate and pathway of CMV transmission to the LBWI who receives a transfusion. Another study goal is to compare or link any CMV infection by either transfused units where the virus was undetected, or filter failure. If CMV disease occurs, the investigators will be able to describe the course and outcome in LBWIs who develop TT-CMV.
Read the detailed description
The primary aim of this birth cohort study is to estimate the incidence of TT-CMV in LBWIs who receive a combination of CMV-seronegative + leukoreduced blood products. That is to say, the effectiveness of the two strategies coupled together will be assessed in the prevention of TT-CMV in at-risk LBWI born to CMV-negative and CMV-positive mothers.
The following hypothesis relates to this primary aim, that the incidence of TT-CMV is elevated in the population of LBWIs born the CMV-positive mothers. According to reports in the literature, breakthrough TT-CMV infection will occur at low rates (< 2.5% incidence) in LBWIs of CMV-negative mothers transfused with seronegative plus leukoreduced blood components.
The secondary aim of this study is to detect CMV DNA and/or elevated residual WBC counts in blood components transfused to LBWIs and to determine whether these results are related to episodes of breakthrough TT-CMV in this study population.
Original sample size considerations were based on estimating and comparing the rates of TT-CMV infection in VLBW infants born to CMV-seropositive mothers or CMV-seronegative mothers. Assuming a 2.55% TT-CMV rate for infants born to CMV-seropositive mothers and a 0.5% TT-CMV rate for infants born to CMV-seronegative mothers, a sample size of 650 infants per group would need to be recruited to detect a difference of approximately 2% in the TT-CMV rate with 80% power (2-sided Fisher's exact test at the 5% significance level).
After three years of accrual and follow-up the incidence of TT-CMV was 0%. Sample size calculations were revised using a 95% confidence interval for a single group of VLBW infants regardless of maternal CMV serostatus. The necessary sample size was 300 transfused VLBW infants based on a one-sided exact 95% confidence interval for a single proportion of 0.0 with an upper bound of 0.01.
- Conditions
- Cytomegalovirus Disease
- Keywords
- Transfusion Transmitted Cytomegalovirus (TT-CMV), Low birthweight infants (LBWIs), Leukoreduction and filter failure, CMV Seronegative blood products
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| LBWIs of CMV-positive mother | LBWIs born to CMV-positive mothers | |
| CMV Sero-negative & Sero-postive LBWIs | LBWIs of CMV sero-negative \& sero-positive mothers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimate the incidence of TT-CMV in LBWIs who receive CMV-seronegative plus leukoreduced blood products.
The effectiveness of these two strategies coupled together will be assessed in the prevention of TT-CMV in at-risk LBWI born to CMV-negative and CMV-positive mothers.
Measured: 90 days study observation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2009 (estimated)
- Study startJan 2010
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus DiseaseStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 600 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Cassandra D Josephson, Emory University
- Investigators
- Cassandra Josephson, MD, Study director, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00907686
- Sponsor's protocol ID
- IRB00014684
- Other IDs
- P01HL086773-01A1, NCT00907686
- Acronym
- TT-CMV
- Status last verified
- Jun 2015
- First submitted
- 21 May 2009
- Last updated
- 26 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Josephson CD, Caliendo AM, Easley KA, Knezevic A, Shenvi N, Hinkes MT, Patel RM, Hillyer CD, Roback JD. Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study. JAMA Pediatr. 2014 Nov;168(11):1054-62. doi: 10.1001/jamapediatrics.2014.1360.
PubMed 25243446Josephson CD, Castillejo MI, Caliendo AM, Waller EK, Zimring J, Easley KA, Kutner M, Hillyer CD, Roback JD. Prevention of transfusion-transmitted cytomegalovirus in low-birth weight infants (</=1500 g) using cytomegalovirus-seronegative and leukoreduced transfusions. Transfus Med Rev. 2011 Apr;25(2):125-32. doi: 10.1016/j.tmrv.2010.11.004. Epub 2011 Feb 23.
PubMed 21345642
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Transfusion-transmitted CMV (TT-CMV) in Lowbirth Weight Infants (LBWI; ≤1500 Grams) Using CMV Seronegative and Leukoreduced Transfusions.
- ClinicalTrials.gov ID
- NCT00907686
- Acronym / sponsor ID
- TT-CMV / IRB00014684
- Conditions
- Cytomegalovirus Disease
- Keywords
- Transfusion Transmitted Cytomegalovirus (TT-CMV), Low birthweight infants (LBWIs), Leukoreduction and filter failure, CMV Seronegative blood products
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 600 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jan 2010
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 22 May 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 spread of viruses through transfusions is the cause of serious illness and death in recipients whose immune systems are unable to fight infection. Another group of patients whose immune systems are underdeveloped and can be affected by a particular virus known as cytomegalovirus (CMV) is low birthweight infants (LBWIs). CMV can be spread through the placenta, during the birth process, through breast milk, while in the hospital or while caring for someone carrying the virus as well as through a transfusion, known as transfusion-transmitted (TT-CMV).
The spread of TT-CMV in LBWIs can be curtailed by transfusing blood products that are CMV negative as well as to filter the white cells in blood that carry the virus (leukoreduction). The purpose of this study is to see if the use of these two strategies can lower the spread of CMV through a transfusion. How "safe" the blood actually is through leukoreduction is not known and CMV still occurs in LBWIs. It is not clear whether this approach is optimal or whether additional safety steps are needed to completely prevent TT-CMV. Specific actions that could tell us when virus has reached the blood product or breast milk is to test each of these to determine if virus slipped "unnoticed" and/or when the product was not thoroughly filtered.
In this study, the investigators believe that the use of both prevention strategies will result in a lower rate of TT-CMV, and that the "cause" of TT-CMV may be found in the presence of CMV at the DNA level or by unfiltered white cells that remain in the blood product. Thus, the most significant clinical question that remains to be addressed is whether this double strategy for transfusion safety actually provides a "zero CMV-risk" blood supply or whether further safety measures (DNA testing + 100% leukoreduction) must be used to protect this extremely vulnerable patient group from CMV infection. This birth cohort study will be done with 6 participating NICUs, and will study both CMV positive and negative mothers in order to estimate the rate and pathway of CMV transmission to the LBWI who receives a transfusion. Another study goal is to compare or link any CMV infection by either transfused units where the virus was undetected, or filter failure. If CMV disease occurs, the investigators will be able to describe the course and outcome in LBWIs who develop TT-CMV.
Detailed description
The primary aim of this birth cohort study is to estimate the incidence of TT-CMV in LBWIs who receive a combination of CMV-seronegative + leukoreduced blood products. That is to say, the effectiveness of the two strategies coupled together will be assessed in the prevention of TT-CMV in at-risk LBWI born to CMV-negative and CMV-positive mothers.
The following hypothesis relates to this primary aim, that the incidence of TT-CMV is elevated in the population of LBWIs born the CMV-positive mothers. According to reports in the literature, breakthrough TT-CMV infection will occur at low rates (< 2.5% incidence) in LBWIs of CMV-negative mothers transfused with seronegative plus leukoreduced blood components.
The secondary aim of this study is to detect CMV DNA and/or elevated residual WBC counts in blood components transfused to LBWIs and to determine whether these results are related to episodes of breakthrough TT-CMV in this study population.
Original sample size considerations were based on estimating and comparing the rates of TT-CMV infection in VLBW infants born to CMV-seropositive mothers or CMV-seronegative mothers. Assuming a 2.55% TT-CMV rate for infants born to CMV-seropositive mothers and a 0.5% TT-CMV rate for infants born to CMV-seronegative mothers, a sample size of 650 infants per group would need to be recruited to detect a difference of approximately 2% in the TT-CMV rate with 80% power (2-sided Fisher's exact test at the 5% significance level).
After three years of accrual and follow-up the incidence of TT-CMV was 0%. Sample size calculations were revised using a 95% confidence interval for a single group of VLBW infants regardless of maternal CMV serostatus. The necessary sample size was 300 transfused VLBW infants based on a one-sided exact 95% confidence interval for a single proportion of 0.0 with an upper bound of 0.01.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LBWIs of CMV-positive mother | – | –LBWIs born to CMV-positive mothers |
| CMV Sero-negative & Sero-postive LBWIs | – | –LBWIs of CMV sero-negative \& sero-positive mothers |
Who may qualify
- Ages
- 1 hour to 5 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Low birthweight infants in NICU.
Key inclusion criteria (2 listed)
- All LBWIs whose weight is ≤ 1500 grams at birth
- LBWI is within first five days of life
Key exclusion criteria (7 listed)
- LBWI not expected to live past first seven days of life
- LBWI has a severe congenital abnormality
- LBWI has received a RBC or platelet transfusion at another institution prior to transfer
- LBWI has received an in-utero transfusion
- LBWI is clinically suspected of having toxoplasmosis, rubella, herpes infection(s) at birth
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Estimate the incidence of TT-CMV in LBWIs who receive CMV-seronegative plus leukoreduced blood products.
Time frame: 90 days study observation
The effectiveness of these two strategies coupled together will be assessed in the prevention of TT-CMV in at-risk LBWI born to CMV-negative and CMV-positive mothers.
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 Jun 2015.
- Derived from this study: PubMed 25243446Josephson CD, Caliendo AM, Easley KA, Knezevic A, Shenvi N, Hinkes MT, Patel RM, Hillyer CD, Roback JD. Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study. JAMA Pediatr. 2014 Nov;168(11):1054-62. doi: 10.1001/jamapediatrics.2014.1360.
- Derived from this study: PubMed 21345642Josephson CD, Castillejo MI, Caliendo AM, Waller EK, Zimring J, Easley KA, Kutner M, Hillyer CD, Roback JD. Prevention of transfusion-transmitted cytomegalovirus in low-birth weight infants (</=1500 g) using cytomegalovirus-seronegative and leukoreduced transfusions. Transfus Med Rev. 2011 Apr;25(2):125-32. doi: 10.1016/j.tmrv.2010.11.004. Epub 2011 Feb 23.
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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.
Cassandra Josephson, MD study director
Emory University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cytomegalovirus Disease, run by Emory University at 3 sites in United States.
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 2 inclusion and 7 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 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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?
Estimate the incidence of TT-CMV in LBWIs who receive CMV-seronegative plus leukoreduced blood products. (time frame: 90 days study observation). 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 NCT00907686, which also lists 2 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 Jun 2015; AzTrials last refreshed its copy on 29 Oct 2026.