Sickle Cell DiseasePhase 4NCT02594462
Contraception in Women With Sickle Cell Disease
A Phase 4 study testing etonogestrel-releasing implant contraceptive in people with Sickle Cell Disease, run by University of Sao Paulo at 2 sites in Brazil.
Trial summary
Sickle cell anemia is a homozygous genetic disease with high prevalence in Brazil. There are changes in conformation and physicochemical properties of red cells that generate varied clinical manifestations among which is chronic hemolytic anemia, cardiovascular diseases, fever, splenic sequestration and usually… Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- etonogestrel-releasing implant contraceptive
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesBrazil
- Study dates
- Jan 2015to Jun 2019
- Phase
- Phase 4
- 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 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women with homozygous sickle cell anemia ( hemoglobin SS ) , who had at least one episode of sickle cell pain crisis in the last three months pre- enrollment.
- Age between 18 and 40 years-old ;
- Desire to use a long-term hormonal contraception
- Agreed to participate in the study after reading and signing the informed consent form.
Who cannot join
- Smoking, alcoholism or drug addiction ;
- Obesity , defined as body mass index (BMI ) greater than or equal to 30 kg / m2 ;
- contraindication to the use of isolated progestogen , according to WHO's eligibility criteria (WHO 2009)
- Desire to maintain standard of cyclic menstrual bleeding ;
- Allergy known local anesthetic ( lidocaine ) , once the implant is inserted after subdermal application of the local anesthetic
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
University of Sao Paulo
Ribeirão Preto, São Paulo, 14049-900
Bahiana School of Medicne and Public Health
Salvador, Estado de Bahia
About this study
Official title: Use of Etonogestrel-releasing Contraceptive Implant in Women With Sickle Cell Disease
Sickle cell anemia is a homozygous genetic disease with high prevalence in Brazil. There are changes in conformation and physicochemical properties of red cells that generate varied clinical manifestations among which is chronic hemolytic anemia, cardiovascular diseases, fever, splenic sequestration and usually painful crises. Women with sickle cell anemia have high maternal-fetal and neonatal morbidity and mortality. During pregnancy, there is intensification of maternal anemia, episodes of painful crises; and also, more obstetric risks, such as pre-eclampsia, thromboembolism and hemorrhage. Thus, there is the need for adequate reproductive family planning for this population conducted mainly through hormonal contraception. The World Health Organization recommends that all contraceptive methods may be prescribed for people with sickle cell anemia women, being the progestogen-only contraceptive methods the most indicated due to no changes in venous or arterial thrombosis. Nevertheless, there is need for further scientific evidence as the best contraceptive choice among women with sickle cell anemia in relation to safety, adhesion and reduction of pain crises. The objective of this study is to evaluate the clinical effect through safety of etonogestrel-releasing contraceptive implant in women with sickle cell anemia during twelve months.
Read the detailed description
There are 3,500 children born each year with sickle cell disease in Brazil. Almost three percent of Bahia population has sickle cell anemia, which is the most prevalent in Brazil (BRAGA, 2007).
Despite the high prevalence of sickle cell disease in our population, the best option Contraceptive for these women is still uncertain, based on low-quality studies (Haddad et al., 2012). Since this is a condition associated with numerous complications such as painful crises, splenic sequestration, marrow aplasia, among others, leads to frequent hospitalizations and high absenteeism rates. Women with sickle cell disease in reproductive age are exposed to non-planning pregnancies, which will cause high risk for maternal mortality (33%), and increased pictures of painful crises, and important maternal and newborn complications such as abortion, childbirth premature, thrombosis, among others (Andemariam, Browning, 2013). Therefore, there is a need to provide them with appropriate methods for effective reproductive planning.
Hormonal contraceptives with only progestogen, such as releasing implant etonogestrel (ENG), representing an option to reduce unwanted pregnancies, especially in patients at risk for venous thrombosis, such as patients with anemia sickle, because it doens´t interfere with the coagulation system (Conrad et al., 2004; Liedaagard etal., 2011). Thus, in addition to avoid an unwanted pregnancy, these methods have impact on reduction of maternal and fetal morbidity and mortality and neonatal known to be associated with pregnancies in women with sickle cell anemia (Santos et al., 2005).
The scientific literature is limited and scarce on the association between use of methods contraceptives in women with sickle cell disease and correlation with clinical complications such as seizures painful and anemia (Haddad et al., 2012).
The contraceptive implant etonogestrel is a reversibly progestogen-only contraceptive method, long lasting, highly effective, with high continuation rate. However, there is still no studies in women with sickle cell anemia in use thereof.
As it is a progestogen-only method, it does not increase the risk of thrombosis and may, as depot medroxyprogesterone acetate (Abood et al., 1997), reducing painful crises, with the advantage of high efficacy and long duration.
In this context, to increase adherence and whether a clinical benefit from use of the implant contraceptive releasing ENG, the contraceptive method more effectively isolated progestogen available in Brazil, in relation to painful crises and anemia among women with sickle cell disease, it is made of fundamental importance the development of a study in a city of high prevalence in Brazil.
- Conditions
- Sickle Cell Disease
- Being tested
- etonogestrel-releasing implant contraceptive
- Keywords
- contraception, Anemia, Sickle Cell
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
etonogestrel-releasing implant contraceptiveDrug
Also called implanon
The etonogestrel implant will be inserted until the fifth day of the menstrual cycle . Anthropometric measurements will be performed , blood pressure measurement , application of pain questionnaire for the last three months, and collection of fasting blood in our clinic . After these measures , the ENG implant will be applied per researcher trained for such a procedure , following the recommendations outlined by the manufacturer. Women are instructed to return after 3, 6, 9, 12 months, fasting 8h , when they will be measured anthropometric measurements , blood collection, and delivery of pain questionnaires and standard of menstrual bleeding.
| Study group | Role | What they receive |
|---|---|---|
| ENG-group | Other | Twenty-five women with homozygous sickle cell anemia (hemoglobin SS), aged between 18-40 years-old, who had at least one episode of sickle cell pain crisis in the last three months pre- enrollment; whom desire to use etonogestrel-releasing implant contraceptive without contraindications will be invited to inserted etonogestrel implant.
Etonogestrel implant is a single implant progestogen-only, with 4 cm in length and 2 mm diameter containing 68 mg etonogestrel (3- ketodesogestrel), the active metabolite of desogestrel, involved in a ethylene vinyl acetate membrane (Huber, 1998), which is released continuously in bloodstream for three years. It will be inserted subdermal, on the inner face of non-dominant arm between the first and seventh day of the menstrual cycle. Receives: Drug: etonogestrel-releasing implant contraceptive |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of pain crises
Self reported of pain quantity on a diary.
Measured: 12 months
Secondary outcomes (2)
Clinical Safety as measured by hemoglobin, hepatic function
Immediately before the implant insertion, peripheral blood samples (20 mL) were collected Blood samples were collected to evaluate complete blood count (reticulocytes, hemoglobin, platelets and leukocytes), hepatic function (Alkaline phosphatase, gamma-glutaryl transferase, amino alanine transferase, aspartate amino transferase, total bilirubin and its fractions), before , 6 and 12 months after the implant insertion.
Measured: 12 months
Pain Scores on the Visual Analog Scale
Pain intensity was measured by a visual scale, scored 0-10 (0=no pain until 10=worst pain) over each 3 months.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2015 (estimated)
- Study startJan 2015
- Primary completionOct 2018
- Study completionJun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Escola Bahiana de Medicina e Saude Publica
- Responsible party
- Principal investigator, Milena Bastos Brito, MD, PhD, University of Sao Paulo
- Investigators
- MILENA B BRITO, MD, PhD, Principal investigator, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02594462
- Sponsor's protocol ID
- 458660
- Status last verified
- Nov 2020
- First submitted
- 11 Jun 2015
- Last updated
- 6 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Etonogestrel-releasing Contraceptive Implant in Women With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT02594462
- Acronym / sponsor ID
- 458660
- Conditions
- Sickle Cell Disease
- Keywords
- contraception, Anemia, Sickle Cell
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- Escola Bahiana de Medicina e Saude Publica
- Study start
- Jan 2015
- Primary completion
- Oct 2018 (actual)
- Study completion
- Jun 2019 (actual)
- First posted
- 3 Nov 2015 (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.
Sickle cell anemia is a homozygous genetic disease with high prevalence in Brazil. There are changes in conformation and physicochemical properties of red cells that generate varied clinical manifestations among which is chronic hemolytic anemia, cardiovascular diseases, fever, splenic sequestration and usually painful crises. Women with sickle cell anemia have high maternal-fetal and neonatal morbidity and mortality. During pregnancy, there is intensification of maternal anemia, episodes of painful crises; and also, more obstetric risks, such as pre-eclampsia, thromboembolism and hemorrhage. Thus, there is the need for adequate reproductive family planning for this population conducted mainly through hormonal contraception. The World Health Organization recommends that all contraceptive methods may be prescribed for people with sickle cell anemia women, being the progestogen-only contraceptive methods the most indicated due to no changes in venous or arterial thrombosis. Nevertheless, there is need for further scientific evidence as the best contraceptive choice among women with sickle cell anemia in relation to safety, adhesion and reduction of pain crises. The objective of this study is to evaluate the clinical effect through safety of etonogestrel-releasing contraceptive implant in women with sickle cell anemia during twelve months.
Detailed description
There are 3,500 children born each year with sickle cell disease in Brazil. Almost three percent of Bahia population has sickle cell anemia, which is the most prevalent in Brazil (BRAGA, 2007).
Despite the high prevalence of sickle cell disease in our population, the best option Contraceptive for these women is still uncertain, based on low-quality studies (Haddad et al., 2012). Since this is a condition associated with numerous complications such as painful crises, splenic sequestration, marrow aplasia, among others, leads to frequent hospitalizations and high absenteeism rates. Women with sickle cell disease in reproductive age are exposed to non-planning pregnancies, which will cause high risk for maternal mortality (33%), and increased pictures of painful crises, and important maternal and newborn complications such as abortion, childbirth premature, thrombosis, among others (Andemariam, Browning, 2013). Therefore, there is a need to provide them with appropriate methods for effective reproductive planning.
Hormonal contraceptives with only progestogen, such as releasing implant etonogestrel (ENG), representing an option to reduce unwanted pregnancies, especially in patients at risk for venous thrombosis, such as patients with anemia sickle, because it doens´t interfere with the coagulation system (Conrad et al., 2004; Liedaagard etal., 2011). Thus, in addition to avoid an unwanted pregnancy, these methods have impact on reduction of maternal and fetal morbidity and mortality and neonatal known to be associated with pregnancies in women with sickle cell anemia (Santos et al., 2005).
The scientific literature is limited and scarce on the association between use of methods contraceptives in women with sickle cell disease and correlation with clinical complications such as seizures painful and anemia (Haddad et al., 2012).
The contraceptive implant etonogestrel is a reversibly progestogen-only contraceptive method, long lasting, highly effective, with high continuation rate. However, there is still no studies in women with sickle cell anemia in use thereof.
As it is a progestogen-only method, it does not increase the risk of thrombosis and may, as depot medroxyprogesterone acetate (Abood et al., 1997), reducing painful crises, with the advantage of high efficacy and long duration.
In this context, to increase adherence and whether a clinical benefit from use of the implant contraceptive releasing ENG, the contraceptive method more effectively isolated progestogen available in Brazil, in relation to painful crises and anemia among women with sickle cell disease, it is made of fundamental importance the development of a study in a city of high prevalence in Brazil.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ENG-group | Other | Drug: etonogestrel-releasing implant contraceptiveTwenty-five women with homozygous sickle cell anemia (hemoglobin SS), aged between 18-40 years-old, who had at least one episode of sickle cell pain crisis in the last three months pre- enrollment; whom desire to use etonogestrel-releasing implant contraceptive without contraindications will be invited to inserted etonogestrel implant. Etonogestrel implant is a single implant progestogen-only, with 4 cm in length and 2 mm diameter containing 68 mg etonogestrel (3- ketodesogestrel), the active metabolite of desogestrel, involved in a ethylene vinyl acetate membrane (Huber, 1998), which is released continuously in bloodstream for three years. It will be inserted subdermal, on the inner face of non-dominant arm between the first and seventh day of the menstrual cycle. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Women with homozygous sickle cell anemia ( hemoglobin SS ) , who had at least one episode of sickle cell pain crisis in the last three months pre- enrollment.
- Age between 18 and 40 years-old ;
- Desire to use a long-term hormonal contraception
- Agreed to participate in the study after reading and signing the informed consent form.
Key exclusion criteria (5 listed)
- Smoking, alcoholism or drug addiction ;
- Obesity , defined as body mass index (BMI ) greater than or equal to 30 kg / m2 ;
- contraindication to the use of isolated progestogen , according to WHO's eligibility criteria (WHO 2009)
- Desire to maintain standard of cyclic menstrual bleeding ;
- Allergy known local anesthetic ( lidocaine ) , once the implant is inserted after subdermal application of the local anesthetic
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 |
|---|---|---|
| etonogestrel-releasing implant contraceptiveAlso: implanonThe etonogestrel implant will be inserted until the fifth day of the menstrual cycle . Anthropometric measurements will be performed , blood pressure measurement , application of pain questionnaire for the last three months, and collection of fasting blood in our clinic . After these measures , the ENG implant will be applied per researcher trained for such a procedure , following the recommendations outlined by the manufacturer. Women are instructed to return after 3, 6, 9, 12 months, fasting 8h , when they will be measured anthropometric measurements , blood collection, and delivery of pain questionnaires and standard of menstrual bleeding. | Drug | ENG-group |
Primary outcome
Number of pain crises
Time frame: 12 months
Self reported of pain quantity on a diary.
2 secondary outcomes
Clinical Safety as measured by hemoglobin, hepatic function
Time frame: 12 months
Pain Scores on the Visual Analog Scale
Time frame: 12 months
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 6 Nov 2020.
- Individual participant dataSharing planned: No
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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.
MILENA B BRITO, MD, PhD principal investigator
University of Sao Paulo
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing etonogestrel-releasing implant contraceptive in people with Sickle Cell Disease, run by University of Sao Paulo at 2 sites in Brazil.
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 4 inclusion and 5 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 6 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Number of pain crises (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Nov 2020.