Splenectomy; StatusNCT03571399
A Nationwide Italian Survey on Asplenia
An observational study of Splenectomy; Status, run by Società Italiana Talassemie ed Emoglobinopatie.
Trial summary
Spleen is involved in several functions, such as the production of protective antibodies, the removal of unwanted particulate matter from the blood (eg bacteria) and also the storing of blood cells, especially white cells and platelets. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Splenectomy; Status
- How many people
- 1,400 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2016to 28 Feb 2017
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: All patients diagnosed with of any type of asplenia (congenital, surgical and functional) will be included in the study.
Who may be able to join
- Adult and pediatric patients affected by asplenia
Who cannot join
- Medical history including all relevant clinical data required by the protocol not available
About this study
Official title: Mortality and Morbidity in a Large Cohort of Asplenic Patients: a Nationwide Survey From the Italian Network on Asplenia
Spleen is involved in several functions, such as the production of protective antibodies, the removal of unwanted particulate matter from the blood (eg bacteria) and also the storing of blood cells, especially white cells and platelets. Asplenia is a status due to spleen absence or dysfunction, which results from several rare diseases. Congenital Asplenia is a condition with absent or dysfunctional spleen, associated with other congenital abnormalities; functional asplenia is a status with present but dysfunctional spleen, related to many rare diseases, such as sickle cell disease, thalassemia, essential thrombocythaemia, lymphoproliferative diseases and splenectomy is the surgical removal of the spleen in order to treat a huge number of rare hematological and oncological diseases. So, asplenia is the final result of a numerous variety of rare disorders, and it leads to a high risk of infections and thrombotic events with significant mortality and morbidity. Antibiotic prophylaxis and specific vaccinations are recommended in this high risk population but adherence was shown to be very poor. A national register was demonstrated to improve population outcomes and reduce health care costs and facilitate research and public health purposes in this target population. In Europe very little experience exists in comprehensive national program for management of asplenia, and only in a restricted part of England and in Ireland surveys of post-splenectomized patients have been performed. In Italy no common policy of patient care has yet been developed, and management of asplenia is mainly case or locally directed.
Read the detailed description
People with asplenia have a high risk of serious infections, as the spleen is a reservoir of naive B and T cells and functions as a filter for antigens and capsulated bacteria in the blood. It also removes aged blood cells and Howell-Jolly's bodies from red blood cells.
The asplenia can be congenital, surgical and functional. Congenital asplenia is a condition associated with rare and poorly understood and studied syndromes. Surgical asplenia consists in the removal of the spleen for the management of some hematological or oncological diseases. Functional asplenia characterizes numerous hematological and non-hematological diseases; the most representative, among those hematological, is the sickle cell disease (SCD), among the non-hematological causes of functional asplenia, include several autoimmune diseases (e.g. Lupus, Sjogrens), inflammatory bowel disease (e.g. celiac disease, Crohn's disease, ulcerative rectocolitis ) and infiltrative diseases (e.g. amyloidosis, sarcoidosis).
Infections are the leading cause of death in individuals with asplenia, especially in children under the age of five . It has been shown that the integrity of the splenic function is necessary for the development and survival of IgM memory cells, a population of memory B cells of IgM isotype. These interesting data would explain the increased susceptibility to invasive infections sustained by capsulated bacteria in subjects with anatomical or functional asplenia, especially in the first years of life, in which there is a physiological and transient IgM memory deficit, supporting the common knowledge that the spleen represents a particular immunological environment that is fundamental for the removal of polysaccharide antigens and for the optimal antibody response.
In asplenic subjects, Streptococcus pneumoniae, Hemophilus influenzae and Neisseria meningitidis are the germs that most frequently cause invasive infections, such as bacteremia, sepsis and meningitis; therefore it is clear that prevention and immediate and aggressive treatment are the cornerstone of the correct management of this group of patients. Recently the new 13-valent conjugate vaccine against pneumococcus has been introduced and it is believed that this is a new and more effective strategy to reduce the infectious risk in these subjects; however, specific data on the population of asplenic subjects are lacking.
Recent studies and reports have shown a greater incidence of thrombotic complications in asplenic subjects, even if the rate of thrombotic events seems to be different between the different pathologies underlying the condition of asplenia. In fact, a large number of thrombotic events have been observed in splenectomized subjects for hereditary spherocytosis, for thalassemia, idiopathic thrombocytopenia purpura and other hematological diseases but the pathophysiological basis of these complications, the possible preventive treatments are not yet known. effective and optimal management of thrombotic events. Furthermore, preliminary data suggest a different susceptibility to infectious and thrombotic complications in the different forms of asplenia. If this is confirmed, the indications for antibiotic and antithrombotic prophylaxis, the timing of monitoring and the more or less aggressive management of complications, could vary in the different forms of asplenia.
Moreover, in Italy there are no shared and homogeneous indications on the prevention and treatment of short and long-term complications related to the condition of asplenia and their knowledge is still very limited among the medical staff. It has been shown that countries that have adopted shared measures for the management of these patients have achieved an improvement in the prevention of complications, through an increase vaccination coverage even among adults and the continuous information on possible risks related to the clinical condition. In fact, it often happens that patients do not respond to regular follow-up missing vaccination recalls and reducing over time all information about their health. This occurrence was considered one of the major risk factors for the development of serious complications in asplenic individuals .
The aim of the study is to retrospectively and prospectively assess a relatively large population of patients with asplenia in order to identify the rate of mortality and morbidity (infectious and thrombotic complications) developed by asplenic patients during the observation period.
- Conditions
- Splenectomy; Status
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of the causes of mortality and morbidity
The infectious and the thrombotic complication developed by asplenic patients during the observation period will be assessed
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2018
- Study start1 Mar 2016
- Primary completion1 Mar 2016
- Study completion28 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Splenectomy; StatusStudies of the same condition, open and under way.
- 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
- Cross-sectional
- Enrolment
- 1,400 participants (actual)
Sponsor and investigators
- Lead sponsor
- Società Italiana Talassemie ed Emoglobinopatie
- Sponsor type
- University, hospital or other
- Collaborators
- University of Campania Luigi Vanvitelli
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03571399
- Sponsor's protocol ID
- Asplenia
- Status last verified
- May 2018
- First submitted
- 7 Jun 2018
- Last updated
- 28 Jun 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Quinn CT, Rogers ZR, Buchanan GR. Survival of children with sickle cell disease. Blood. 2004 Jun 1;103(11):4023-7. doi: 10.1182/blood-2003-11-3758. Epub 2004 Feb 5.
PubMed 14764527Lee A, Thomas P, Cupidore L, Serjeant B, Serjeant G. Improved survival in homozygous sickle cell disease: lessons from a cohort study. BMJ. 1995 Dec 16;311(7020):1600-2. doi: 10.1136/bmj.311.7020.1600.
PubMed 8555802Gill FM, Sleeper LA, Weiner SJ, Brown AK, Bellevue R, Grover R, Pegelow CH, Vichinsky E. Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease. Blood. 1995 Jul 15;86(2):776-83.
PubMed 7606007Kruetzmann S, Rosado MM, Weber H, Germing U, Tournilhac O, Peter HH, Berner R, Peters A, Boehm T, Plebani A, Quinti I, Carsetti R. Human immunoglobulin M memory B cells controlling Streptococcus pneumoniae infections are generated in the spleen. J Exp Med. 2003 Apr 7;197(7):939-45. doi: 10.1084/jem.20022020.
PubMed 12682112Sullivan JL, Ochs HD, Schiffman G, Hammerschlag MR, Miser J, Vichinsky E, Wedgwood RJ. Immune response after splenectomy. Lancet. 1978 Jan 28;1(8057):178-81. doi: 10.1016/s0140-6736(78)90612-8.
PubMed 74605Pearson HA, Spencer RP, Cornelius EA. Functional asplenia in sickle-cell anemia. N Engl J Med. 1969 Oct 23;281(17):923-6. doi: 10.1056/NEJM196910232811703. No abstract available.
PubMed 5811425Hongeng S, Wilimas JA, Harris S, Day SW, Wang WC. Recurrent Streptococcus pneumoniae sepsis in children with sickle cell disease. J Pediatr. 1997 May;130(5):814-6. doi: 10.1016/s0022-3476(97)80026-1.
PubMed 9152293Casale M, Perrotta S. Splenectomy for hereditary spherocytosis: complete, partial or not at all? Expert Rev Hematol. 2011 Dec;4(6):627-35. doi: 10.1586/ehm.11.51.
PubMed 22077527Jais X, Ioos V, Jardim C, Sitbon O, Parent F, Hamid A, Fadel E, Dartevelle P, Simonneau G, Humbert M. Splenectomy and chronic thromboembolic pulmonary hypertension. Thorax. 2005 Dec;60(12):1031-4. doi: 10.1136/thx.2004.038083. Epub 2005 Aug 5.
PubMed 16085731Waghorn DJ. Overwhelming infection in asplenic patients: current best practice preventive measures are not being followed. J Clin Pathol. 2001 Mar;54(3):214-8. doi: 10.1136/jcp.54.3.214.
PubMed 11253134Hosea SW, Burch CG, Brown EJ, Berg RA, Frank MM. Impaired immune response of splenectomised patients to polyvalent pneumococcal vaccine. Lancet. 1981 Apr 11;1(8224):804-7. doi: 10.1016/s0140-6736(81)92681-7.
PubMed 6111673Wright J, Thomas P, Serjeant GR. Septicemia caused by Salmonella infection: an overlooked complication of sickle cell disease. J Pediatr. 1997 Mar;130(3):394-9. doi: 10.1016/s0022-3476(97)70201-4.
PubMed 9063414Taher AT, Musallam KM, Karimi M, El-Beshlawy A, Belhoul K, Daar S, Saned MS, El-Chafic AH, Fasulo MR, Cappellini MD. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood. 2010 Mar 11;115(10):1886-92. doi: 10.1182/blood-2009-09-243154. Epub 2009 Dec 23.
PubMed 20032507
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mortality and Morbidity in a Large Cohort of Asplenic Patients: a Nationwide Survey From the Italian Network on Asplenia
- ClinicalTrials.gov ID
- NCT03571399
- Acronym / sponsor ID
- Asplenia
- Conditions
- Splenectomy; Status
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,400 participants (actual)
- Lead sponsor
- Società Italiana Talassemie ed EmoglobinopatieUniversity, hospital or other
- Collaborators
- University of Campania Luigi Vanvitelli
- Study start
- 1 Mar 2016 (actual)
- Primary completion
- 1 Mar 2016 (actual)
- Study completion
- 28 Feb 2017 (actual)
- First posted
- 27 Jun 2018 (actual)
- 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.
Spleen is involved in several functions, such as the production of protective antibodies, the removal of unwanted particulate matter from the blood (eg bacteria) and also the storing of blood cells, especially white cells and platelets. Asplenia is a status due to spleen absence or dysfunction, which results from several rare diseases. Congenital Asplenia is a condition with absent or dysfunctional spleen, associated with other congenital abnormalities; functional asplenia is a status with present but dysfunctional spleen, related to many rare diseases, such as sickle cell disease, thalassemia, essential thrombocythaemia, lymphoproliferative diseases and splenectomy is the surgical removal of the spleen in order to treat a huge number of rare hematological and oncological diseases. So, asplenia is the final result of a numerous variety of rare disorders, and it leads to a high risk of infections and thrombotic events with significant mortality and morbidity. Antibiotic prophylaxis and specific vaccinations are recommended in this high risk population but adherence was shown to be very poor. A national register was demonstrated to improve population outcomes and reduce health care costs and facilitate research and public health purposes in this target population. In Europe very little experience exists in comprehensive national program for management of asplenia, and only in a restricted part of England and in Ireland surveys of post-splenectomized patients have been performed. In Italy no common policy of patient care has yet been developed, and management of asplenia is mainly case or locally directed.
Detailed description
People with asplenia have a high risk of serious infections, as the spleen is a reservoir of naive B and T cells and functions as a filter for antigens and capsulated bacteria in the blood. It also removes aged blood cells and Howell-Jolly's bodies from red blood cells.
The asplenia can be congenital, surgical and functional. Congenital asplenia is a condition associated with rare and poorly understood and studied syndromes. Surgical asplenia consists in the removal of the spleen for the management of some hematological or oncological diseases. Functional asplenia characterizes numerous hematological and non-hematological diseases; the most representative, among those hematological, is the sickle cell disease (SCD), among the non-hematological causes of functional asplenia, include several autoimmune diseases (e.g. Lupus, Sjogrens), inflammatory bowel disease (e.g. celiac disease, Crohn's disease, ulcerative rectocolitis ) and infiltrative diseases (e.g. amyloidosis, sarcoidosis).
Infections are the leading cause of death in individuals with asplenia, especially in children under the age of five . It has been shown that the integrity of the splenic function is necessary for the development and survival of IgM memory cells, a population of memory B cells of IgM isotype. These interesting data would explain the increased susceptibility to invasive infections sustained by capsulated bacteria in subjects with anatomical or functional asplenia, especially in the first years of life, in which there is a physiological and transient IgM memory deficit, supporting the common knowledge that the spleen represents a particular immunological environment that is fundamental for the removal of polysaccharide antigens and for the optimal antibody response.
In asplenic subjects, Streptococcus pneumoniae, Hemophilus influenzae and Neisseria meningitidis are the germs that most frequently cause invasive infections, such as bacteremia, sepsis and meningitis; therefore it is clear that prevention and immediate and aggressive treatment are the cornerstone of the correct management of this group of patients. Recently the new 13-valent conjugate vaccine against pneumococcus has been introduced and it is believed that this is a new and more effective strategy to reduce the infectious risk in these subjects; however, specific data on the population of asplenic subjects are lacking.
Recent studies and reports have shown a greater incidence of thrombotic complications in asplenic subjects, even if the rate of thrombotic events seems to be different between the different pathologies underlying the condition of asplenia. In fact, a large number of thrombotic events have been observed in splenectomized subjects for hereditary spherocytosis, for thalassemia, idiopathic thrombocytopenia purpura and other hematological diseases but the pathophysiological basis of these complications, the possible preventive treatments are not yet known. effective and optimal management of thrombotic events. Furthermore, preliminary data suggest a different susceptibility to infectious and thrombotic complications in the different forms of asplenia. If this is confirmed, the indications for antibiotic and antithrombotic prophylaxis, the timing of monitoring and the more or less aggressive management of complications, could vary in the different forms of asplenia.
Moreover, in Italy there are no shared and homogeneous indications on the prevention and treatment of short and long-term complications related to the condition of asplenia and their knowledge is still very limited among the medical staff. It has been shown that countries that have adopted shared measures for the management of these patients have achieved an improvement in the prevention of complications, through an increase vaccination coverage even among adults and the continuous information on possible risks related to the clinical condition. In fact, it often happens that patients do not respond to regular follow-up missing vaccination recalls and reducing over time all information about their health. This occurrence was considered one of the major risk factors for the development of serious complications in asplenic individuals .
The aim of the study is to retrospectively and prospectively assess a relatively large population of patients with asplenia in order to identify the rate of mortality and morbidity (infectious and thrombotic complications) developed by asplenic patients during the observation period.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All patients diagnosed with of any type of asplenia (congenital, surgical and functional) will be included in the study.
Key inclusion criteria (1 listed)
- Adult and pediatric patients affected by asplenia
Key exclusion criteria (1 listed)
- Medical history including all relevant clinical data required by the protocol not available
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
Identification of the causes of mortality and morbidity
Time frame: 10 years
The infectious and the thrombotic complication developed by asplenic patients during the observation period will be assessed
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 28 Jun 2018.
- Background: PubMed 14764527Quinn CT, Rogers ZR, Buchanan GR. Survival of children with sickle cell disease. Blood. 2004 Jun 1;103(11):4023-7. doi: 10.1182/blood-2003-11-3758. Epub 2004 Feb 5.
- Background: PubMed 8555802Lee A, Thomas P, Cupidore L, Serjeant B, Serjeant G. Improved survival in homozygous sickle cell disease: lessons from a cohort study. BMJ. 1995 Dec 16;311(7020):1600-2. doi: 10.1136/bmj.311.7020.1600.
- Background: PubMed 7606007Gill FM, Sleeper LA, Weiner SJ, Brown AK, Bellevue R, Grover R, Pegelow CH, Vichinsky E. Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease. Blood. 1995 Jul 15;86(2):776-83.
- Background: PubMed 12682112Kruetzmann S, Rosado MM, Weber H, Germing U, Tournilhac O, Peter HH, Berner R, Peters A, Boehm T, Plebani A, Quinti I, Carsetti R. Human immunoglobulin M memory B cells controlling Streptococcus pneumoniae infections are generated in the spleen. J Exp Med. 2003 Apr 7;197(7):939-45. doi: 10.1084/jem.20022020.
- Background: PubMed 74605Sullivan JL, Ochs HD, Schiffman G, Hammerschlag MR, Miser J, Vichinsky E, Wedgwood RJ. Immune response after splenectomy. Lancet. 1978 Jan 28;1(8057):178-81. doi: 10.1016/s0140-6736(78)90612-8.
- Background: PubMed 5811425Pearson HA, Spencer RP, Cornelius EA. Functional asplenia in sickle-cell anemia. N Engl J Med. 1969 Oct 23;281(17):923-6. doi: 10.1056/NEJM196910232811703. No abstract available.
- Background: PubMed 9152293Hongeng S, Wilimas JA, Harris S, Day SW, Wang WC. Recurrent Streptococcus pneumoniae sepsis in children with sickle cell disease. J Pediatr. 1997 May;130(5):814-6. doi: 10.1016/s0022-3476(97)80026-1.
- Background: PubMed 22077527Casale M, Perrotta S. Splenectomy for hereditary spherocytosis: complete, partial or not at all? Expert Rev Hematol. 2011 Dec;4(6):627-35. doi: 10.1586/ehm.11.51.
- Background: PubMed 16085731Jais X, Ioos V, Jardim C, Sitbon O, Parent F, Hamid A, Fadel E, Dartevelle P, Simonneau G, Humbert M. Splenectomy and chronic thromboembolic pulmonary hypertension. Thorax. 2005 Dec;60(12):1031-4. doi: 10.1136/thx.2004.038083. Epub 2005 Aug 5.
- Background: PubMed 11253134Waghorn DJ. Overwhelming infection in asplenic patients: current best practice preventive measures are not being followed. J Clin Pathol. 2001 Mar;54(3):214-8. doi: 10.1136/jcp.54.3.214.
- Background: PubMed 6111673Hosea SW, Burch CG, Brown EJ, Berg RA, Frank MM. Impaired immune response of splenectomised patients to polyvalent pneumococcal vaccine. Lancet. 1981 Apr 11;1(8224):804-7. doi: 10.1016/s0140-6736(81)92681-7.
- Background: PubMed 9063414Wright J, Thomas P, Serjeant GR. Septicemia caused by Salmonella infection: an overlooked complication of sickle cell disease. J Pediatr. 1997 Mar;130(3):394-9. doi: 10.1016/s0022-3476(97)70201-4.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Splenectomy; Status, run by Società Italiana Talassemie ed Emoglobinopatie.
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 1 inclusion and 1 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 28 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
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?
Identification of the causes of mortality and morbidity (time frame: 10 years). 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 NCT03571399, which also lists 13 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 28 Jun 2018.