Thrombotic Thrombocytopenic PurpuraROSCAPLINCT05785468
A Retrospective, Observational Study on the Response to Caplacizumab Treatment in aTTP Patients: the Italian Experience (ROSCAPLI)
An observational study of Thrombotic Thrombocytopenic Purpura, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
Thrombotic thrombocytopenic purpura (TTP) is a rare disease with a mortality rate of over 90% if left untreated [1]. TTP is a prototype of the thrombotic microangiopathies (TMAs), and it is characterized by disseminated formation of platelet-rich thrombi in arterioles and capillaries resulting in microangiopathic… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Thrombotic Thrombocytopenic Purpura
- What is being tested?
- Caplacizumab
- How many people
- 1 participants
- Where
- 1 siteItaly
- Study dates
- 21 Oct 2021to 30 Mar 2023
- 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
- No healthy volunteers
- Child, Adult, Older adult
Study population: This study is a multicenter, retrospective, observational study in patients with aTTP treated with PEX in association with caplacizumab, and immunosuppression between Q4-2019 and 28 February2021.The incidence of aTTP has been estimated at 3-11 cases per million people per year [1-3]. Considering that the adult population of Italy is about 45 million, the number of aTTP cases in Italy is approximately 300 per year. Assuming that 15% of the patients are treated at about 20 sites participating in the study and are eligible to participate, approximately 50 patients can be expected to be included in an 18-month period.The clinical signs will be parametrized by the PLASMIC score and the Glasgow score, where calculated in the various centers. The PLASMIC score and the Glasgow score will be evaluated according to the obtained values (0-4, 5-6, and 7; <13 and 13-15, respectively). All the clinical and laboratory parameters will be taken in each center and reported in the CRF.
Who may be able to join
- The patients included in this study should have received caplacizumab for treatment in the period between Q4-2019 and the end of February 2021 while the end of follow up observation is scheduled for Q1-2021 (to observe at least one month of post treatment follow up).
- The diagnosis should be based on either clinical/laboratory parameters inclusive of measurement of ADAMTS13 level <10%) or the PLASMIC score (platelets, lysis, active cancer, stem cell or solid organ transplant, MCV, INR, and creatinine) with intermediate and high risk (sore>5) already computed or retrospectively calculated as previously detailed [19] for centers that did not measure the ADAMTS13 level.
Who cannot join
- Patients treated with uncertain aTTP diagnosis according to the above inclusion criteria - Patients manifesting clinical signs like aTTP but characterized by a different pathogenesis (e.g. cancer, sepsis)
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
FPG
Roma, 00168
Raimondo De Cristofaro, 0630156329, raimondo.decristofaro@policlinicogemelli.it
About this study
Thrombotic thrombocytopenic purpura (TTP) is a rare disease with a mortality rate of over 90% if left untreated [1]. TTP is a prototype of the thrombotic microangiopathies (TMAs), and it is characterized by disseminated formation of platelet-rich thrombi in arterioles and capillaries resulting in microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and potential end-organ injury mainly involving the brain, heart, and kidneys leading to significant morbidity/mortality
Read the detailed description
Thrombotic thrombocytopenic purpura (TTP) is a rare disease with a mortality rate of over 90% if left untreated [1]. TTP is a prototype of the thrombotic microangiopathies (TMAs), and it is characterized by disseminated formation of platelet-rich thrombi in arterioles and capillaries resulting in microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and potential end-organ injury mainly involving the brain, heart, and kidneys leading to significant morbidity/mortality. TTP can either be hereditary or acquired, and the pathogenesis of the latter consists of autoimmune antibodies against the metalloproteinase "a disintegrin and metalloproteinase with a thrombospondin type 1 motif (ADAMTS13)", and ADAMTS13 is responsible for the cleavage of ultra-large multimers of von Willebrand factor (vWF), which induces activation of platelets through glycoprotein Ib-alpha (GPIb-α) receptors and the activated A1 domain of the VWF multimers without a trigger-like endothelial damage or tissue factor. Acquired TTP (aTTP) can be primary (idiopathic) or secondary to some underlying disorders. Therapeutic plasma exchange (PEX) is the mainstay of treatment of aTTP, and with the introduction of PEX, the mortality rate declined dramatically below 20% [1]. The rationale of PEX is the replacement of ADAMTS13, and removal of ultra-large vWF and anti ADAMTS13 antibodies. In newly diagnosed patients with aTTP, PEX and corticosteroids are usually started upfront together [3]. However, a subset of patients may remain refractory to this treatment or have an initial response but relapse after the discontinuation of PEX during the follow-up. There is limited information or consensus available on the management of relapsed/refractory aTTP. While managing PEX refractory patients, PEX may be intensified to 1.5 plasma volume (PV), and even twice daily PEX can be used [4]. In patients remaining refractory to PEX plus corticosteroids, the administration of high-dose methylprednisolone 1 g per day for 3 days can be the choice of treatment [5].Other treatment options in patients with relapsed/refractory TTP may include rituximab, vincristine, cyclophosphamide, cyclosporine A, and splenectomy[6-8]. Caplacizumab is fully reimbursed by the National Health System in Italy since January 2020. While observational data have recently been published in other countries, such as Germany, on the efficacy and safety of caplacizumab [18], cumulative data deriving from the Italian centers that manage the therapy of TTP with caplacizumab have not yet been collected. The aim of this proposal is, therefore,to collect retrospective observationaldata on the response to caplacizumab treatment in patients with aTTP treated with this drug in Italy during the Q4-2019 and Q1-2021.
- Conditions
- Thrombotic Thrombocytopenic Purpura
- Being tested
- Caplacizumab
- Medical subject headings
- Purpura, Thrombotic Thrombocytopenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaplacizumabDrug
description and quantification of clinical response in terms of platelet count recovery in patients with aTTP treated t with caplacizumab
What is being measured
The primary outcome is the main question the study is designed to answer.
description and quantification of clinical response in terms of platelet count recovery in patients with aTTP treated t with caplacizumab
The primary objective in this study is the description of clinical response in terms of platelet count recovery in patients with aTTP treated with caplacizumab , in addition to PEX and immunosuppression in the real-world setting.
Measured: 18 months
The primary objective in this study is the quantification of clinical response in terms of platelet count recovery in patients with aTTP treated t with caplacizumab
The primary objective in this study is the quantification of clinical response in terms of platelet count recovery in patients with aTTP treated with caplacizumab , in addition to PEX and immunosuppression in the real-world setting.
Measured: 18 months
Secondary outcomes (5)
evaluation of number of exacerbations,rate of relapse and TTP-related mortality
Secondary objectives include:
- Number of exacerbations, defined as recurrent thrombocytopenia within 30 days after the end of therapy;
Measured: 18 months
evaluation of number of exacerbations,rate of relapse and TTP-related mortality
Secondary objectives include:
- Rate of relapse, defined as a TTP event occurring more than 30 days after the end of daily plasma exchange;
Measured: 18 months
evaluation of number of exacerbations,rate of relapse and TTP-related mortality
Secondary objectives include:
- Refractoriness; defined by the lack of a doubling of platelet count after 4 days of treatment and a lactate dehydrogenase level that remained above the upper limit of the normal range
Measured: 18 months
evaluation of number of exacerbations,rate of relapse and TTP-related mortality
Secondary objectives include:
- TTP-related mortality
Measured: 18 months
evaluation of number of exacerbations,rate of relapse and TTP-related mortality
Secondary objectives include:
- Evaluation of adverse events
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2023
- Study start21 Oct 2021
- Primary completion30 Mar 2023 (estimated)
- Study completion30 Mar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thrombotic Thrombocytopenic PurpuraStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe 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
- Retrospective
- Enrolment
- 1 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, De Cristofaro Raimondo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05785468
- Sponsor's protocol ID
- 4305
- Acronym
- ROSCAPLI
- Status last verified
- Mar 2023
- First submitted
- 27 Feb 2023
- Last updated
- 27 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Retrospective, Observational Study on the Response to Caplacizumab Treatment in aTTP Patients: the Italian Experience (ROSCAPLI)
- ClinicalTrials.gov ID
- NCT05785468
- Acronym / sponsor ID
- ROSCAPLI / 4305
- Conditions
- Thrombotic Thrombocytopenic Purpura
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 21 Oct 2021 (actual)
- Primary completion
- 30 Mar 2023 (estimated)
- Study completion
- 30 Mar 2023 (estimated)
- First posted
- 27 Mar 2023 (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.
Thrombotic thrombocytopenic purpura (TTP) is a rare disease with a mortality rate of over 90% if left untreated [1]. TTP is a prototype of the thrombotic microangiopathies (TMAs), and it is characterized by disseminated formation of platelet-rich thrombi in arterioles and capillaries resulting in microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and potential end-organ injury mainly involving the brain, heart, and kidneys leading to significant morbidity/mortality
Detailed description
Thrombotic thrombocytopenic purpura (TTP) is a rare disease with a mortality rate of over 90% if left untreated [1]. TTP is a prototype of the thrombotic microangiopathies (TMAs), and it is characterized by disseminated formation of platelet-rich thrombi in arterioles and capillaries resulting in microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and potential end-organ injury mainly involving the brain, heart, and kidneys leading to significant morbidity/mortality. TTP can either be hereditary or acquired, and the pathogenesis of the latter consists of autoimmune antibodies against the metalloproteinase "a disintegrin and metalloproteinase with a thrombospondin type 1 motif (ADAMTS13)", and ADAMTS13 is responsible for the cleavage of ultra-large multimers of von Willebrand factor (vWF), which induces activation of platelets through glycoprotein Ib-alpha (GPIb-α) receptors and the activated A1 domain of the VWF multimers without a trigger-like endothelial damage or tissue factor. Acquired TTP (aTTP) can be primary (idiopathic) or secondary to some underlying disorders. Therapeutic plasma exchange (PEX) is the mainstay of treatment of aTTP, and with the introduction of PEX, the mortality rate declined dramatically below 20% [1]. The rationale of PEX is the replacement of ADAMTS13, and removal of ultra-large vWF and anti ADAMTS13 antibodies. In newly diagnosed patients with aTTP, PEX and corticosteroids are usually started upfront together [3]. However, a subset of patients may remain refractory to this treatment or have an initial response but relapse after the discontinuation of PEX during the follow-up. There is limited information or consensus available on the management of relapsed/refractory aTTP. While managing PEX refractory patients, PEX may be intensified to 1.5 plasma volume (PV), and even twice daily PEX can be used [4]. In patients remaining refractory to PEX plus corticosteroids, the administration of high-dose methylprednisolone 1 g per day for 3 days can be the choice of treatment [5].Other treatment options in patients with relapsed/refractory TTP may include rituximab, vincristine, cyclophosphamide, cyclosporine A, and splenectomy[6-8]. Caplacizumab is fully reimbursed by the National Health System in Italy since January 2020. While observational data have recently been published in other countries, such as Germany, on the efficacy and safety of caplacizumab [18], cumulative data deriving from the Italian centers that manage the therapy of TTP with caplacizumab have not yet been collected. The aim of this proposal is, therefore,to collect retrospective observationaldata on the response to caplacizumab treatment in patients with aTTP treated with this drug in Italy during the Q4-2019 and Q1-2021.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- This study is a multicenter, retrospective, observational study in patients with aTTP treated with PEX in association with caplacizumab, and immunosuppression between Q4-2019 and 28 February2021.The incidence of aTTP has been estimated at 3-11 cases per million people per year [1-3]. Considering that the adult population of Italy is about 45 million, the number of aTTP cases in Italy is approximately 300 per year. Assuming that 15% of the patients are treated at about 20 sites participating in the study and are eligible to participate, approximately 50 patients can be expected to be included in an 18-month period.The clinical signs will be parametrized by the PLASMIC score and the Glasgow score, where calculated in the various centers. The PLASMIC score and the Glasgow score will be evaluated according to the obtained values (0-4, 5-6, and 7; <13 and 13-15, respectively). All the clinical and laboratory parameters will be taken in each center and reported in the CRF.
Key inclusion criteria (2 listed)
- The patients included in this study should have received caplacizumab for treatment in the period between Q4-2019 and the end of February 2021 while the end of follow up observation is scheduled for Q1-2021 (to observe at least one month of post treatment follow up).
- The diagnosis should be based on either clinical/laboratory parameters inclusive of measurement of ADAMTS13 level <10%) or the PLASMIC score (platelets, lysis, active cancer, stem cell or solid organ transplant, MCV, INR, and creatinine) with intermediate and high risk (sore>5) already computed or retrospectively calculated as previously detailed [19] for centers that did not measure the ADAMTS13 level.
Key exclusion criteria (1 listed)
- Patients treated with uncertain aTTP diagnosis according to the above inclusion criteria - Patients manifesting clinical signs like aTTP but characterized by a different pathogenesis (e.g. cancer, sepsis)
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 |
|---|---|---|
| Caplacizumabdescription and quantification of clinical response in terms of platelet count recovery in patients with aTTP treated t with caplacizumab | Drug | – |
Primary outcome
description and quantification of clinical response in terms of platelet count recovery in patients with aTTP treated t with caplacizumab
Time frame: 18 months
The primary objective in this study is the description of clinical response in terms of platelet count recovery in patients with aTTP treated with caplacizumab , in addition to PEX and immunosuppression in the real-world setting.
The primary objective in this study is the quantification of clinical response in terms of platelet count recovery in patients with aTTP treated t with caplacizumab
Time frame: 18 months
The primary objective in this study is the quantification of clinical response in terms of platelet count recovery in patients with aTTP treated with caplacizumab , in addition to PEX and immunosuppression in the real-world setting.
5 secondary outcomes
evaluation of number of exacerbations,rate of relapse and TTP-related mortality
Time frame: 18 months
evaluation of number of exacerbations,rate of relapse and TTP-related mortality
Time frame: 18 months
evaluation of number of exacerbations,rate of relapse and TTP-related mortality
Time frame: 18 months
evaluation of number of exacerbations,rate of relapse and TTP-related mortality
Time frame: 18 months
evaluation of number of exacerbations,rate of relapse and TTP-related mortality
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2023.
- Individual participant dataSharing planned: Undecided
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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.
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 Thrombotic Thrombocytopenic Purpura, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
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 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: status not confirmed, as of the sponsor's last update on 27 Mar 2023. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Raimondo De Cristofaro, MD (0630156329, raimondo.decristofaro@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
description and quantification of clinical response in terms of platelet count recovery in patients with aTTP treated t with caplacizumab (time frame: 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Mar 2023.