TY - JOUR
T1 - The EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases (TREAT-SVDs) trial: Study protocol for a randomised crossover trial
AU - Kopczak, A.
AU - Stringer, M.S.
AU - van den Brink, H.
AU - Kerkhofs, D.
AU - Blair, G.W.
AU - van Dinther, M.
AU - Onkenhout, L.
AU - Wartolowska, K.A.
AU - Thrippleton, M.J.
AU - Duering, M.
AU - Staals, J.
AU - Middeke, M.
AU - Andre, E.
AU - Norrving, B.
AU - Bousser, M.G.
AU - Mansmann, U.
AU - Rothwell, P.M.
AU - Doubal, F.N.
AU - van Oostenbrugge, R.
AU - Biessels, G.J.
AU - Webb, A.J.S.
AU - Wardlaw, J.M.
AU - Dichgans, M.
AU - SVDs@Target Investigators
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Background: Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs. Aims: To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and whether losartan has a beneficial effect when compared to atenolol in patients with symptomatic SVDs. Design: TREAT-SVDs is an investigator-led, prospective, open-label, randomised crossover trial with blinded endpoint assessment (PROBE design) conducted at five study sites across Europe. Patients aged 18 years or older with symptomatic SVD who have an indication for antihypertensive treatment and are suffering from either sporadic SVD and a history of lacunar stroke or vascular cognitive impairment (group A) or CADASIL (group B) are randomly allocated 1:1:1 to one of three sequences of antihypertensive treatment. Patients stop their regular antihypertensive medication for a 2-week run-in period followed by 4-week periods of monotherapy with amlodipine, losartan and atenolol in random order as open-label medication in standard dose. Outcomes: The primary outcome measure is cerebrovascular reactivity (CVR) as determined by blood oxygen level dependent brain MRI signal response to hypercapnic challenge with change in CVR in normal appearing white matter as primary endpoint. Secondary outcome measures are mean systolic blood pressure (BP) and BP variability (BPv). Discussion: TREAT-SVDs will provide insights into the effects of different antihypertensive drugs on CVR, BP, and BPv in patients with symptomatic sporadic and hereditary SVDs. Funding: European Union's Horizon 2020 programme.
AB - Background: Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs. Aims: To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and whether losartan has a beneficial effect when compared to atenolol in patients with symptomatic SVDs. Design: TREAT-SVDs is an investigator-led, prospective, open-label, randomised crossover trial with blinded endpoint assessment (PROBE design) conducted at five study sites across Europe. Patients aged 18 years or older with symptomatic SVD who have an indication for antihypertensive treatment and are suffering from either sporadic SVD and a history of lacunar stroke or vascular cognitive impairment (group A) or CADASIL (group B) are randomly allocated 1:1:1 to one of three sequences of antihypertensive treatment. Patients stop their regular antihypertensive medication for a 2-week run-in period followed by 4-week periods of monotherapy with amlodipine, losartan and atenolol in random order as open-label medication in standard dose. Outcomes: The primary outcome measure is cerebrovascular reactivity (CVR) as determined by blood oxygen level dependent brain MRI signal response to hypercapnic challenge with change in CVR in normal appearing white matter as primary endpoint. Secondary outcome measures are mean systolic blood pressure (BP) and BP variability (BPv). Discussion: TREAT-SVDs will provide insights into the effects of different antihypertensive drugs on CVR, BP, and BPv in patients with symptomatic sporadic and hereditary SVDs. Funding: European Union's Horizon 2020 programme.
KW - Small vessel diseases
KW - lacunar stroke
KW - vascular cognitive impairment
KW - CADASIL
KW - cerebrovascular reactivity
KW - blood pressure variability
KW - antihypertensive drug classes
KW - amlodipine
KW - magnetic resonance imaging
KW - randomised clinical trial
KW - CEREBROVASCULAR REACTIVITY
KW - LACUNAR STROKE
KW - HYPERTENSION
KW - BLOCKERS
KW - DEMENTIA
KW - RISK
U2 - 10.1177/23969873221143570
DO - 10.1177/23969873221143570
M3 - Article
C2 - 37021189
SN - 2396-9873
JO - European Stroke Journal
JF - European Stroke Journal
ER -