Cerebral Amyloid Angiopathy, Intracerebral Hemorrhage Lobar
Conditions
Keywords
Cerebral Amyloid Angiopathy, Intracerebral Hemorrhage, Colchicine, Recurrence
Brief summary
The goal of this clinical trial is to assess the safety and tolerability of colchicine for preventing intracerebral haemorrhage (ICH) recurrence in patients with cerebral amyloid angiopathy (CAA)-ICH at high risk of recurrence. The main questions it aims to answer are: * Is colchicine safe for CAA-ICH patients? * Is colchicine well tolerated for CAA-ICH patients? Researchers will compare colchicine to a placebo (a look-alike substance that contains no drug) to see if colchicine is safe and tolerable for CAA-ICH patients and works to prevent ICH recurrence. Participants will: * Take colchicine or a placebo every day for 12 months * Receive telephone follow-ups at 3 and 9 months, and visit the clinic at 6 and 12 months for checkups and tests * Control blood pressure and improve lifestyle
Detailed description
The CARE-ICH study is a multicenter, randomized, double-blind, placebo-controlled, phase II trial. The primary objective of the CARE-ICH study is to assess the safety and tolerability of colchicine for preventing ICH recurrence in patients with CAA-ICH at high risk of recurrence, as well as provide a preliminary estimate of the feasibility and efficacy for planning a phase III trial. Patients with CAA-ICH and a high risk of recurrence-defined as 1 prior symptomatic ICH and presence of cortical superficial siderosis, or ≥2 prior symptomatic ICHs-within 3 months of their most recent ICH will be enrolled and randomized in a 1:1 ratio to receive either oral colchicine 0.5 mg once per day or matching placebo for 1 year, in addition to standard care, including blood pressure control and lifestyle modifications. Follow-up visits will take place at 3, 6, 9, and 12 months. Each visit will include assessments of adverse events, medication adherence, and clinical outcomes. The primary outcomes are the incidence of treatment-emergent adverse events and treatment tolerability.
Interventions
DRUGColchicine 0.5mg
Oral colchicine 0.5mg once per day combined with standard treatment
DRUGMatching placebo
Oral matching placebo once per day combined with standard treatment
Sponsors
Peking Union Medical College Hospital
West China Hospital
Huashan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
Double-blind, randomized, placebo-controlled, phase II pilot study
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥55 years; * Diagnosed with probable CAA with supporting pathology or probable CAA according to the modified Boston criteria (version 1.5); * High risk of recurrent ICH, defined as: 1 prior symptomatic ICH and presence of cortical superficial siderosis (cSS), or ≥2 prior symptomatic ICHs; * Time interval since symptom onset of the most recent ICH: ≤3 months (earlier enrollment is preferred if criteria are met); * Modified Rankin Scale (mRS) score ≤4 at randomization; * Written informed consent from the participant or their legally authorized representative before study enrollment.
Exclusion criteria
* Secondary causes of ICH; * Pre-existing moderate-to-severe renal, liver or blood disorders (anaemia \[hemoglobin \<10g/dL\], thrombocytopaenia \[platelet count \<100×109/L\], leucopenia \[white blood cell \<3×109/L\], cirrhosis or severe hepatic dysfunction, renal insufficiency \[estimated glomerular filtration rate (eGFR) \<15mL/min\]); * Prior diagnosis of gout, peripheral neuropathy, myopathy, inflammatory bowel disease or chronic diarrhea; * Concurrent treatment with regular immune-suppressant (corticosteroids, cyclophosphamide, azathioprine, mycophenolate mofetil, rituximab), moderate-to-strong CYP3A4 inhibitors (atazanavir, clarithromycin, darunavir/ritonavir, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, tipranavir/ritonavir) or P-glycoprotein inhibitors (cyclosporine, ranolazine); * Known allergy, sensitivity or intolerance to colchicine; * Contraindications or inability to complete brain MRI or susceptibility weighted imaging (SWI) scans; * Pregnancy or breastfeeding; * Recent participation in any other interventional study in the past 30 days before enrollment; * Not expected to survive the follow-up period; * Inability to adhere to study procedures; * Any condition in which investigators believe that participating in this study may be harmful to the patient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment emergent adverse events (TEAE) | Any time within 1 year | Incidence of treatment emergent adverse events (TEAE) |
| Frequency of participants who are adherence to medicine without permanent discontinuation due to TEAE until the end of follow-up. | 1 year | Frequency of participants who are adherence to medicine without permanent discontinuation due to TEAE until the end of follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety-TEAE according to Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 | Any time within 1 year | TEAE according to Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 |
| Feasibility-Recruitment rate | 1 year | The mean number of participants randomized per site per year |
| Feasibility-Retention rate | 1 year | Randomized participants who completed 1-year follow-up |
| Clinical efficacy-Recurrent symptomatic spontaneous lobar ICH | Any time within 1 year | A new non-traumatic lobar ICH lesion confirmed on SWI or CT with corresponding symptoms |
| Clinical efficacy-Composite of major adverse cardiovascular events (MACE) | Any time within 1 year | Stroke (ischemic, hemorrhagic or undefined), myocardial infarction, revascularization procedure for coronary, carotid or peripheral arterial disease, and vascular death |
| Clinical efficacy-Any individual MACE | Any time within 1 year | Stroke (ischemic, hemorrhagic or undefined), myocardial infarction, revascularization procedure for coronary, carotid or peripheral arterial disease, and vascular death |
| Clinical efficacy-Cognitive outcome | 1 year | Cognitive function assessed by the Montreal Cognitive Assessment (MoCA) (The total score ranges from 0 to 30, with higher scores indicating better cognitive function) |
| Safety-Treatment-related adverse events (TRAE) | Any time within 1 year | An AE assessed as having a causal relationship to the study product, and be classified as definitely, probably or possibly related AEs |
| Radiological efficacy-Severe cSS progression | 1 year | ≥2 new cSS foci on 1-year SWI scan |
| Radiological efficacy-Any cSS progression | 1 year | ≥1 new cSS foci on 1-year SWI scan |
| Radiological efficacy-CMB progression | 1 year | ≥5 new CMBs on 1-year SWI scan |
| Clinical efficacy-Functional outcome | 3-month, 6-month and 1-year | Functional outcome assessed by the modified Rankin scale (mRS) \[mRS score ranges from 0 (no symptom) to 6 (death) and higher score means worse functional outcome\] |
| Clinical efficacy-Quality of life | 1 year | Quality of life assessed by the EuroQol Five-Dimension Five-Level (EQ-5D-5L) questionnaire, which consists of two parts. The descriptive system evaluates health across five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on five levels of severity, where higher levels indicate more severe problems. The visual analogue scale is rated from 0 (worst imaginable health state) to 100 (best imaginable health state), representing the patient's self-rated overall health. |
| Clinical efficacy-Blood inflammatory markers | 6 month and 1 year | High-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). |
| Radiological efficacy-New asymptomatic ICH lesion | 1 year | A new hemorrhagic lesion confirmed on SWI at 1-year, which was absent on SWI at baseline and was not associated with any acute neurological deficit |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory outcomes-Blood-brain barrier permeability | 1 year | Water exchange rate (kw) measured by diffusion-prepared pseudocontinuous arterial spin labeling (DP-pCASL) imaging |
| Exploratory outcomes-Glymphatic function | 1 year | The index for diffusivity along the perivascular space (ALPS index) measured by diffusion tensor imaging |
| Exploratory outcomes-Neuroinflammation pattern | 1 year | The standardized uptake value ratio of 18F-DPA-714 measured by translocator protein (TSPO)-PET |
Countries
China
Contacts
Primary ContactXin Cheng, MD, PhD
Outcome results
None listed