The ConNeCT Study: Neurological Complications of TTP

Thrombotic Thrombocytopenic Purpura Clinical Trial

Official title:

The ConNeCT Study: Neurological Complications of Thrombotic Thrombocytopenic Purpura

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04981028
• Other study ID #: 5988
• Status: Recruiting
• Start date: June 25, 2020
• Est. completion date: June 25, 2022

Study information

• Verified date: July 2021
• Source: Liverpool University Hospitals NHS Foundation Trust
• Contact: Tina Dutt
• Phone: 01512826724
• Email: tina.dutt[@]liverpoolft.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Thrombotic thrombocytopenic purpura (TTP) is a rare condition, which has a very high risk of death if not recognised and given immediate treatment. TTP is caused by a very low level of an enzyme in the body, called ADAMTS13. A lack of ADAMTS13 causes multiple small clots to form around the body which can disrupt the blood flow to important organs. Although survival has improved significantly, it is now being recognised that patients with TTP may suffer with longer term complications as a result of their condition; literature from the USA reports higher rates of major depression and also poor memory and reduced concentration in patients with TTP. The investigators aim to improve the understanding of the long-term complications and review, for the first time, forward-looking data at multiple time points in patients with TTP in the UK. Both patients with a new diagnosis and patients with a known diagnosis of TTP identified in NHS hospitals will be included, over a minimum duration of 2 years. This will be a questionnaire based study with both doctor led and participant led questionnaires at pre-determined points in time. By improving the understanding and comparing symptoms to that of the general population, the investigators hope to improve the support and tailor the treatments which can be offered to patients with TTP.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: June 25, 2022
• Est. primary completion date: June 25, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1.Acute episode TTP:

• Adult male or female patient =18 years of age at the time of signing the consent form, with a confirmed diagnosis of TTP (initial or relapse) based on ADAMTS13 <10% 2. Known

diagnosis of TTP:

• Adult male or female patient = 18 years of age at time of signing the consent form, with a historical confirmed diagnosis of TTP (based on ADAMTS13 at initial

presentation <10%) 3. Healthy control:

• Non-blood relative / friend / carer of patients under the care of Haematology clinics at the Royal Liverpool University hospital or other participating centres.

Exclusion Criteria:

1. Acute episode of TTP:

• Participants less than 18 years old at the time of signing the consent form
• Patient with ADAMTS13 greater than 10%
• Patient with cancer or transplant associated MAHA will not be included
• Patient (or NOK, where patient does not have capacity) not wishing to consent to trial

2. Known diagnosis of TTP:

• Participants less than 18 years old at the time of signing the consent form
• Patient with ADAMTS13 greater than 10%
• Patient with cancer or transplant associated MAHA will not be included
• Patient (or NOK, where patient does not have capacity) not wishing to consent to trial

3. For healthy control:

• Participants less than 18 years old at the time of signing the consent form
• Participant not wishing to consent to trial
• Any personal or family history of thrombotic microangiopathy

Related Conditions & MeSH terms

• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombotic Thrombocytopenic
• Thrombotic Thrombocytopenic Purpura

Intervention

Other:
• Questionnaires (including PHQ-9, TYM and SF-36)
For the acute group, a questionnaire is completed on neurological symptoms at presentation plus specific questions to include brain imaging performed, treatments received and whether they survived the hospital admission (AQ1). There will be a healthcare practitioner led questionnaire (AQ2) and 3 patient led questionnaires (PHQ-9, TYM and SF-36) plus a supplementary questionnaire (AQ3) completed at 1 week, 1 month, 3 months, 6 months and 12 months following diagnosis. For the chronic TTP group, participants will have a questionnaire completed (CQ1) and 3 patient-led questionnaires (PHQ-9, TYM and SF-36) plus a supplementary questionnaire (CQ2). Where neurological symptoms are present, questionnaires will be completed 6 monthly; where there are no neurological symptoms questionnaires are completed every 12 months. The healthy volunteers will complete participant led questionnaires (namely PHQ-9, TYM, SF-36) plus a supplementary baseline questionnaire at two time points 12 months apart.

Locations

Country	Name	City	State
United Kingdom	Royal Liverpool University Hospital	Liverpool

Sponsors (1)

Lead Sponsor	Collaborator
Liverpool University Hospitals NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The percentage of patients with TTP with neurological complications at acute presentation	The primary outcome is to estimate the proportion of both new acute and remission TTP patients developing neurological conditions. These will be reported as counts and percentages with 95% confidence intervals. If we recruit 100 patients in both groups, acute and remission, then we can estimate prevalence rates of 10% with an accuracy of +/- 6%, a 20% prevalence with an accuracy of +/-8% and a 40% prevalence with an accuracy of +/-10%.	1 week, 1 month, 3 months, 6 months, 12 months
Primary	The percentage of patients with TTP in remission with long-term neurological complications	The primary outcome is to estimate the proportion of both new acute and remission TTP patients developing neurological conditions. These will be reported as counts and percentages with 95% confidence intervals. If we recruit 100 patients in both groups, acute and remission, then we can estimate prevalence rates of 10% with an accuracy of +/- 6%, a 20% prevalence with an accuracy of +/-8% and a 40% prevalence with an accuracy of +/-10%.	6 months, 12 months, 18 months, 2 years
Secondary	The percentage of 'follow-up' patients with TTP with a depressive disorder, based on PHQ-9 scoring system, compared to the general UK population.	Secondary outcomes include proportion of TTP patients developing depressive or neurological symptoms or having reduced quality of life. These will be reported using counts and percentages, along with 95% confidence intervals. Also, these outcomes will be compared with the corresponding outcomes from the general population (control group). However, as the study is not powered to detect between group differences no formal hypothesis tests will be undertaken and the data will be presented using summary statistics, counts, percentages and 95% confidence intervals.	6 month, 12 months, 18 months, 2 years
Secondary	The percentage of 'follow-up' patients with TTP with neurocognitive deficit, based on TYM scoring system, compared to the general UK population.	Secondary outcomes include proportion of TTP patients developing depressive or neurological symptoms or having reduced quality of life. These will be reported using counts and percentages, along with 95% confidence intervals. Also, these outcomes will be compared with the corresponding outcomes from the general population (control group). However, as the study is not powered to detect between group differences no formal hypothesis tests will be undertaken and the data will be presented using summary statistics, counts, percentages and 95% confidence intervals.	6 month, 12 months, 18 months, 2 years
Secondary	The percentage of 'follow-up' patients with TTP with reduced quality of life, based on SF-36 score, compared to the general UK population.	Secondary outcomes include proportion of TTP patients developing depressive or neurological symptoms or having reduced quality of life. These will be reported using counts and percentages, along with 95% confidence intervals. Also, these outcomes will be compared with the corresponding outcomes from the general population (control group). However, as the study is not powered to detect between group differences no formal hypothesis tests will be undertaken and the data will be presented using summary statistics, counts, percentages and 95% confidence intervals.	6 month, 12 months, 18 months, 2 years