The ConNeCT Study: Neurological Complications of TTP

• Conditions: Thrombotic Thrombocytopenic Purpura
• Interventions: Other: Questionnaires (including PHQ-9, TYM and SF-36)

• Registration Number: NCT04981028
• Lead Sponsor: Liverpool University Hospitals NHS Foundation Trust

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-06-25
• Status Verified: 2021-07
• Study First Submitted: 2021-07-21
• Study First Submitted QC: 2021-07-21
• Study First Posted: 2021-07-28
• Last Update Submitted: 2021-08-02
• Last Update Posted: 2021-08-09
• Primary Completion: 2022-06-25
• Study Completion: 2022-06-25

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 250

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.

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with known diagnosis of TTP	Questionnaires (including PHQ-9, TYM and SF-36)	Any adult patients with a previously confirmed diagnosis of TTP (more than 12 months ago) based on an ADAMTS13 enzyme level \<10% at initial diagnosis
Healthy volunteers	Questionnaires (including PHQ-9, TYM and SF-36)	Non-blood relative / friend / carer
Patients with acute episode of thrombotic thrombocytopenic purpura (TTP)	Questionnaires (including PHQ-9, TYM and SF-36)	Any adult patients with a suspected diagnosis of TTP (defined by low platelets and anaemia with evidence of red cell breakdown) and confirmed by a low ADAMTS13 enzyme level \<10%

Primary Outcome Measures

Name	Time	Method
The percentage of patients with TTP with neurological complications at acute presentation	1 week, 1 month, 3 months, 6 months, 12 months	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%.
The percentage of patients with TTP in remission with long-term neurological complications	6 months, 12 months, 18 months, 2 years	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%.

Secondary Outcome Measures

Name	Time	Method
The percentage of 'follow-up' patients with TTP with a depressive disorder, based on PHQ-9 scoring system, compared to the general UK population.	6 month, 12 months, 18 months, 2 years	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.
The percentage of 'follow-up' patients with TTP with neurocognitive deficit, based on TYM scoring system, compared to the general UK population.	6 month, 12 months, 18 months, 2 years	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.
The percentage of 'follow-up' patients with TTP with reduced quality of life, based on SF-36 score, compared to the general UK population.	6 month, 12 months, 18 months, 2 years	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.

Trial Locations

Locations (1)

Royal Liverpool University Hospital; 🇬🇧 Liverpool, United Kingdom