<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03001739</url>
  </required_header>
  <id_info>
    <org_study_id>20160920-9</org_study_id>
    <nct_id>NCT03001739</nct_id>
  </id_info>
  <brief_title>Intensive Blood PRessure Control in Patients With Acute Type B AortIc Dissection</brief_title>
  <acronym>RAID</acronym>
  <official_title>Intensive Blood PRessure Control in Patients With Acute Type B AortIc Dissection (RAID): Study Protocol for Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sir Run Run Shaw Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sir Run Run Shaw Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aortic dissection (AD) aneurysm is a common catastrophic aortic disease in clinical setting.&#xD;
      Conservative therapy of heart rate and blood pressure control in the acute phase is the&#xD;
      essential treatment as guidelines recommended. Nevertheless, there is no unanimous optimal&#xD;
      target for blood pressure in patients with AD so far. The American Heart Association and the&#xD;
      Canadian Cardiovascular Society recommend the blood pressure should be controlled to lower&#xD;
      than 140/90mmHg, while for patients with diabetes or chronic renal failure, the blood&#xD;
      pressure target should be no less than 130/80 mmHg. Recently, the Japanese Circulation&#xD;
      Society recommended that the blood pressure should be controlled to no less than 130mmHg.&#xD;
      However, there was few large-scale, randomized, controlled studies reported on the effect of&#xD;
      different blood pressure control levels on the prognosis of patients with AD. Hence, the&#xD;
      intensive control of blood pressure to &lt;120 mmHg, compared to &lt;140 mmHg, may improve the&#xD;
      patients' outcome. Thus, in this study, the effect of intensive blood pressure control&#xD;
      (&lt;120mmHg) with conventional blood pressure control (&lt;140mmHg) on the prognosis of ABAD&#xD;
      patients will be compared, and to identify the therapeutic efficacy of intensive blood&#xD;
      pressure control on the ABAD patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aortic dissection (AD) aneurysm is a common catastrophic aortic disease in clinical setting.&#xD;
      In the U.S., the prevalence is approximate 2.9-3.5 cases/100000 persons per year, with recent&#xD;
      evidence showing an increasing incidence of up to 14 cases per 100000 patients per year. AD&#xD;
      aneurysm can be classified into the types of Stanford A and B based on whether the ascending&#xD;
      aorta was being involved. For acute type B aortic dissection (ABAD), which is generally&#xD;
      accounted for one thirds of all aortic dissection and is especially more common among Chinese&#xD;
      due to the suboptimal control of blood pressure. Optimal treatment of ABAD from symptom onset&#xD;
      remains uncertain. Conservative therapy of heart rate and blood pressure control in the acute&#xD;
      phase is the essential treatment for patient without serious complications such as concurrent&#xD;
      mesenteric artery or lower limb arterial embolism. The long-term survival of ABAD is still&#xD;
      low though great improved in medication optimization and surgical repair technique in the&#xD;
      past decades. It was reported that 5-year and 10-year survival rates for ABAD were 60% and&#xD;
      35% respectively. As the development of minimally invasive techniques in recent years, the&#xD;
      endovascular repair procedure has become a routine procedure in the treatment of patient with&#xD;
      ABAD, this rendered an improved prognosis with a 5-year survival rate close to 80%.&#xD;
&#xD;
      Hypertension is well known as the most common cause for AD. The statistics from International&#xD;
      Registry of Acute Aortic Dissection (IRAD) demonstrated that 72.1% of AD patients had a&#xD;
      history of hypertension. The hypertension may aggravate hematoma expansion and results in&#xD;
      serious consequences. Therefore, effectively blood pressure control may alleviate the severe&#xD;
      pain caused by acute AD and lessen the progression of arterial dissection. The control of&#xD;
      hypertension is the primary treatment for acute aortic dissection, and should be maintained&#xD;
      throughout the entire treatment. Currently, all guidelines recommended to decline the&#xD;
      transaortic pressure via controlling the heart rate and blood pressure for AD patient in&#xD;
      acute phase. Theoretically, to control the blood pressure to the minimal level meeting the&#xD;
      sufficient end-organ perfusion can decrease the risk of vessel rupture as much as possible.&#xD;
      Whereas, too much low blood pressure target may increase the mortality of patients. Powell&#xD;
      and his colleague found when the minimum blood pressure increased by 10mmHg (vs. &lt;70 mmHg,&#xD;
      maximal to 120 mmHg) for AD patients, the risk of death decreased by 12% (OR = 0.88, P&#xD;
      &lt;0.001).&#xD;
&#xD;
      Nevertheless, there is no unanimous optimal target for blood pressure in patients with AD so&#xD;
      far. The American Heart Association and the Canadian Cardiovascular Society recommend the&#xD;
      blood pressure should be controlled to lower than 140/90mmHg, while for patients with&#xD;
      diabetes or chronic renal failure, the blood pressure target should be no less than 130/80&#xD;
      mmHg. Recently, the Japanese Circulation Society recommended that the blood pressure should&#xD;
      be controlled to no less than 130mmHg. Hence, the intensive control of blood pressure to &lt;120&#xD;
      mmHg, compared to &lt;140 mmHg, may improve the patients' outcome. Thus, in this study, the&#xD;
      effect of intensive blood pressure control (&lt;120mmHg) with conventional blood pressure&#xD;
      control (&lt;140mmHg) on the prognosis of ABAD patients will be compared.&#xD;
&#xD;
      Methods Study design and setting The study was a prospective randomized controlled trial that&#xD;
      will recruit a maximal of 360 patients in eight tertiary Chinese hospitals over 2 years. All&#xD;
      patients with new diagnosed ABAD in the participating hospitals will be screened for&#xD;
      potential eligibility. The study was approved by the ethics committee of the hospitals&#xD;
      (20160920-9). Written informed consents will be signed by the patients or their legally&#xD;
      authorized representatives. The study was registered in the website of ClinicalTrial.gov .&#xD;
&#xD;
      Sites and patients Doctors from eight hospitals attended the kick-off meeting held in&#xD;
      Courtyard Marriott, Hangzhou, March 19th, 2016, and discussed the research protocol and&#xD;
      details. The amended research protocol was passed according to revised discussion results and&#xD;
      the agreement of all participating units. The methods of blood pressure measurement and the&#xD;
      apparatus used are unified. All hospitals will adopt similar non-invasive blood pressure&#xD;
      monitoring method and unified monitoring frequency to observe whether the blood pressure is&#xD;
      controlled within the target range in two groups. Likewise, the blood pressure target after&#xD;
      discharge was maintained at the same levels.&#xD;
&#xD;
      All patients with AD from the participating hospitals who conform to the following inclusion&#xD;
      and exclusion criteria will be randomized. Inclusion and exclusion criteria were shown in&#xD;
      other parts.&#xD;
&#xD;
      Randomization Blocked randomization was adopted and the intensive and conventional blood&#xD;
      pressure control treatments were allocated at random in a ratio of 1:1 in blocks of sizes of&#xD;
      4,6,8, and 10 to 360 subjects. The study is an open label trial. After investigators in each&#xD;
      participating centers screened the potential patients within 4 hours after acute onset, a&#xD;
      number from a pre-allocated envelope will be gotten and which denotes which group the patient&#xD;
      will be allocated to.&#xD;
&#xD;
      Treatments All the patients were admitted to ICU or general wards at the discretion of&#xD;
      doctors. Based on the guidelines of aortic management, all patients received analgesic&#xD;
      therapy and standard control of heart rate and blood pressure treatments. Intravenous esmolol&#xD;
      was used for continuous control of heart rates. Choice of intravenous antihypertensive agents&#xD;
      was at the discretion of the in charge physicians. After the stabilization of the situation,&#xD;
      the intravenous medications were shifted to the oral treatments. The target blood pressure&#xD;
      for the intensive and conventional groups were &lt;140mmHg and &lt;120mmHg respectively. For most&#xD;
      patients, they will undergo an endovascular treatment approximate two weeks later.&#xD;
&#xD;
      Study endpoints The primary outcome is a composite in-hospital adverse outcome, including&#xD;
      death, permanent paraplegia or semi- paralysis during the hospitalization, and renal failure&#xD;
      requiring hemodialysis at discharge.&#xD;
&#xD;
      The secondary outcomes include the mortality in 6-month and 1-year, ICU length of stay, total&#xD;
      length of hospital stay, postoperative renal injury, and re- intervention.&#xD;
&#xD;
      Data collection Research coordinators of individual participating hospital will collect the&#xD;
      required data on the case report form. However, the data was de-named and special security&#xD;
      code was required to access the data. To facilitate the communications between investigators,&#xD;
      the case report form was written in Chinese. The primary research institute is responsible&#xD;
      for collecting and checking the data of all centers; and will contact the co-investigators in&#xD;
      various centers for checking or revising should they had any question. The primary research&#xD;
      institute has established an independent study quality control group to implement the&#xD;
      disposal plan for all unexpected circumstances that may occur.&#xD;
&#xD;
      Sample size calculation and interim analysis The primary outcome was a composite in-hospital&#xD;
      adverse outcome, including the death, stroke, permanent paraplegia or semi- paralysis during&#xD;
      the hospitalization, and renal failure requiring hemodialysis at discharge. Bashir et al&#xD;
      reported that the incidence of comprehensive nosocomial severe prognostic adverse events of&#xD;
      ABAD was 45.2%. Assume that the incidence of severe prognosis adverse event in comprehensive&#xD;
      hospital after intensive blood pressure control could be reduced to 30%, so a total of 322&#xD;
      subjects enrolled in the study are sufficient to find the difference statistically between&#xD;
      two groups through the appropriate software calculation under the power of 0.8 and at the&#xD;
      two-side test with α = 0.05. Considering a dropout rate of 10%, it is proposed to include 360&#xD;
      cases totally into the study. A formal interim analysis was conducted halfway during study&#xD;
      enrollment. The overall type I error was controlled using an O'Brien-Fleming spending&#xD;
      function, with a final significance level of 0.05 for the primary end point.&#xD;
&#xD;
      Statistical analysis Descriptive data were reported as either mean ± SD, median&#xD;
      (interquartile range) or number and percentage. With respect to the differences between two&#xD;
      groups, categorical variables were compared using chi-square analysis. Continuous variables&#xD;
      were compared using Independent Sample T test for normally distributed data and Mann-Whitney&#xD;
      U test for non-normally distributed data. For survival analyses, Kaplan-Meier estimates were&#xD;
      generated to assess differences between groups using the log-rank test, and expressed the&#xD;
      data as cumulative mortality curves. Statistical analysis was performed by using SPSS 16.0&#xD;
      (Chicago, Ill, USA) and PASS 11.0. Statistical significance was defined as a P value &lt;0.05.&#xD;
&#xD;
      Discussion ABAD comprises approximately 30% of all aortic dissection cases. In contrast with&#xD;
      type A aortic dissection, patients with type B dissection are tend to be older, have higher&#xD;
      rates of atherosclerosis. Initial goals for acute aortic dissection management are directed&#xD;
      at control of blood pressure and heart rate, which subsequently limiting propagation of the&#xD;
      false lumen by controlling aortic shear stress. Whilst medical management has demonstrated an&#xD;
      in-hospital mortality rate less than 10%, post-discharge the acute type B aortic disease&#xD;
      continues to evolve eventually resulting in complicated type B disease. Moreover, complicated&#xD;
      acute type B aortic dissection shows even more striking mortality as high as 30%,&#xD;
      particularly in the elderly. Poor control of blood pressure was believed to be one of the&#xD;
      main reasons for the progress of the type B aortic dissection into complications or even the&#xD;
      laceration extended to the ascending aorta. Dalsart and colleague demonstrated that a&#xD;
      systolic blood pressure more than 130 mmHg was associated with a bigger aortic enlargement in&#xD;
      type B aortic dissection (P=0.02) . In another study of 25 years follow-up in 252 patients&#xD;
      who received repair of acute type A aortic dissection, patients who maintained a systolic&#xD;
      blood pressure &lt;120 mm Hg had improved freedom from reoperation, compared to those target&#xD;
      blood pressure 120-140 mm Hg or &gt;140 mm Hg. Hence, most guidelines recommended a reasonable&#xD;
      initial target for systolic blood pressure is between 100 and 120 mm Hg. However, this target&#xD;
      is based on the hypothesis that all the end-organs blood supply is not compromised. Data from&#xD;
      International Registry of Acute Aortic Dissection (IRAD) has shown that approximately one&#xD;
      quarter of patients presenting with acute type B aortic dissection are followed into&#xD;
      complicated category, including malperfusion of spinal arteries leading to paresis, and&#xD;
      paraplegia or malperfusion of visceral arteries leading to abdominal pain. Thus, how to&#xD;
      balance the decrease of blood pressure to the lowest amount and maintain adequate end-organ&#xD;
      perfusion is a challenge. Given vast majority patients with type B aortic dissection had a&#xD;
      history of hypertension, a too lower target of blood pressure may comprise the cerebral&#xD;
      perfusion or complicated organ perfusion, which consequently caused stroke or other morbidity&#xD;
      such as ischemic intestinal necrosis. On the other hand, a much strict blood pressure target&#xD;
      and sometimes constrain on the patients daily activities may aggravate patients' worry, which&#xD;
      inversely increased increase the blood pressure. Unfortunately, there is no empirical data or&#xD;
      trials to guide the optimal blood pressure target setting for various patients. Hence, the&#xD;
      study was designed to bridge the gap.&#xD;
&#xD;
      In conclusion, the investigators believe that the study will provide new insight into the of&#xD;
      blood pressure management of patients of acute Type B aortic dissection and subsequently&#xD;
      improve the outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">July 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>composite in-hospital adverse outcome</measure>
    <time_frame>From date of randomization until the date of death from any cause，or permanent paraplegia or semi- paralysis during the hospitalization, and renal failure requiring hemodialysis at discharge, whichever came first, assessed up to 3 months</time_frame>
    <description>including death, permanent paraplegia or semi- paralysis during the hospitalization, and renal failure requiring hemodialysis at discharge</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>mortality</measure>
    <time_frame>6-month and 1-year after onset of the dissection</time_frame>
    <description>All cause mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>From date of ICU admission until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>re-operation or another endovascular intervention for the same problem</measure>
    <time_frame>From date of first intervention until the date of second intervention, assessed up to 12 months</time_frame>
    <description>any intervention for the same situation such as operation or endovascular intervention</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">360</enrollment>
  <condition>Blood High Pressure</condition>
  <condition>Aortic Dissection Type B</condition>
  <arm_group>
    <arm_group_label>Intensive BP control (&lt;120mmHg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Urapidil Hydrochloride Injection (100-400ug/min) or other antihypertensive agents to decrease the BP to &lt; 120 mm Hg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional BP control (120-140mmHg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Urapidil Hydrochloride Injection (100-400ug/min) or other antihypertensive agents to decrease the BP to 120-140 mm Hg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Urapidil Hydrochloride Injection</intervention_name>
    <description>Urapidil Hydrochloride Injection or other antihypertensive agents to decrease the BP to the target level.</description>
    <arm_group_label>Conventional BP control (120-140mmHg)</arm_group_label>
    <arm_group_label>Intensive BP control (&lt;120mmHg)</arm_group_label>
    <other_name>Urapidil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newly diagnosed patients with Stanford type B acute aortic dissection and systolic&#xD;
             blood pressure&gt;160mmHg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt;18 years,&#xD;
&#xD;
          -  In pregnancy,&#xD;
&#xD;
          -  Diagnosis of aortic dissection was made 48 hours or more prior,&#xD;
&#xD;
          -  Dissection due to aortic intramural hematoma or penetrating atherosclerotic ulcer,&#xD;
&#xD;
          -  With history of previous surgical or interventional endovascular treatment for aortic&#xD;
             diseases,&#xD;
&#xD;
          -  With traumatic aortic injury,&#xD;
&#xD;
          -  With history of cerebrovascular accident, brain surgery, chronic renal insufficiency,&#xD;
             and mesenteric vascular thrombosis or dissection,&#xD;
&#xD;
          -  AD patient concomitant with new cerebral infarction, or ischemic mesenteric artery or&#xD;
             lower limb arteries which requiring urgent surgical interventions,&#xD;
&#xD;
          -  With obvious contraindications for antihypertensive therapy, such as severe carotid&#xD;
             stenosis, cerebral infarction in acute phase ,&#xD;
&#xD;
          -  Pathogenesis of the dissection was due to congenital aortic hypoplasia, such as Marfan&#xD;
             syndrome, connective tissue diseases.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yun-song Yu, MD</last_name>
    <role>Study Director</role>
    <affiliation>Zhejiang University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ying-zhi Fang, MD</last_name>
    <phone>+86 571 86006987</phone>
  </overall_contact>
  <location>
    <facility>
      <name>Sir Run Run Shaw Hospital</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310016</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ying-zhi Fang</last_name>
      <phone>+86 571 86006987</phone>
    </contact>
    <investigator>
      <last_name>Yun-song Yu, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 10, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <last_update_submitted>December 20, 2016</last_update_submitted>
  <last_update_submitted_qc>December 20, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 23, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sir Run Run Shaw Hospital</investigator_affiliation>
    <investigator_full_name>Jian-cang Zhou M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aortic Dissection</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urapidil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03001739
org study id: 20160920-9
nct id: NCT03001739
lead sponsor: 
has dmc: Yes
Aortic dissection (AD) aneurysm is a common catastrophic aortic disease in clinical setting.
      Conservative therapy of heart rate and blood pressure control in the acute phase is the
      essential treatment as guidelines recommended. Nevertheless, there is no unanimous optimal
      target for blood pressure in patients with AD so far. The American Heart Association and the
      Canadian Cardiovascular Society recommend the blood pressure should be controlled to lower
      than 140/90mmHg, while for patients with diabetes or chronic renal failure, the blood
      pressure target should be no less than 130/80 mmHg. Recently, the Japanese Circulation
      Society recommended that the blood pressure should be controlled to no less than 130mmHg.
      However, there was few large-scale, randomized, controlled studies reported on the effect of
      different blood pressure control levels on the prognosis of patients with AD. Hence, the
      intensive control of blood pressure to <120 mmHg, compared to <140 mmHg, may improve the
      patients' outcome. Thus, in this study, the effect of intensive blood pressure control
      (<120mmHg) with conventional blood pressure control (<140mmHg) on the prognosis of ABAD
      patients will be compared, and to identify the therapeutic efficacy of intensive blood
      pressure control on the ABAD patients.
Aortic dissection (AD) aneurysm is a common catastrophic aortic disease in clinical setting.
      In the U.S., the prevalence is approximate 2.9-3.5 cases/100000 persons per year, with recent
      evidence showing an increasing incidence of up to 14 cases per 100000 patients per year. AD
      aneurysm can be classified into the types of Stanford A and B based on whether the ascending
      aorta was being involved. For acute type B aortic dissection (ABAD), which is generally
      accounted for one thirds of all aortic dissection and is especially more common among Chinese
      due to the suboptimal control of blood pressure. Optimal treatment of ABAD from symptom onset
      remains uncertain. Conservative therapy of heart rate and blood pressure control in the acute
      phase is the essential treatment for patient without serious complications such as concurrent
      mesenteric artery or lower limb arterial embolism. The long-term survival of ABAD is still
      low though great improved in medication optimization and surgical repair technique in the
      past decades. It was reported that 5-year and 10-year survival rates for ABAD were 60% and
      35% respectively. As the development of minimally invasive techniques in recent years, the
      endovascular repair procedure has become a routine procedure in the treatment of patient with
      ABAD, this rendered an improved prognosis with a 5-year survival rate close to 80%.

      Hypertension is well known as the most common cause for AD. The statistics from International
      Registry of Acute Aortic Dissection (IRAD) demonstrated that 72.1% of AD patients had a
      history of hypertension. The hypertension may aggravate hematoma expansion and results in
      serious consequences. Therefore, effectively blood pressure control may alleviate the severe
      pain caused by acute AD and lessen the progression of arterial dissection. The control of
      hypertension is the primary treatment for acute aortic dissection, and should be maintained
      throughout the entire treatment. Currently, all guidelines recommended to decline the
      transaortic pressure via controlling the heart rate and blood pressure for AD patient in
      acute phase. Theoretically, to control the blood pressure to the minimal level meeting the
      sufficient end-organ perfusion can decrease the risk of vessel rupture as much as possible.
      Whereas, too much low blood pressure target may increase the mortality of patients. Powell
      and his colleague found when the minimum blood pressure increased by 10mmHg (vs. <70 mmHg,
      maximal to 120 mmHg) for AD patients, the risk of death decreased by 12% (OR = 0.88, P
      <0.001).

      Nevertheless, there is no unanimous optimal target for blood pressure in patients with AD so
      far. The American Heart Association and the Canadian Cardiovascular Society recommend the
      blood pressure should be controlled to lower than 140/90mmHg, while for patients with
      diabetes or chronic renal failure, the blood pressure target should be no less than 130/80
      mmHg. Recently, the Japanese Circulation Society recommended that the blood pressure should
      be controlled to no less than 130mmHg. Hence, the intensive control of blood pressure to <120
      mmHg, compared to <140 mmHg, may improve the patients' outcome. Thus, in this study, the
      effect of intensive blood pressure control (<120mmHg) with conventional blood pressure
      control (<140mmHg) on the prognosis of ABAD patients will be compared.

      Methods Study design and setting The study was a prospective randomized controlled trial that
      will recruit a maximal of 360 patients in eight tertiary Chinese hospitals over 2 years. All
      patients with new diagnosed ABAD in the participating hospitals will be screened for
      potential eligibility. The study was approved by the ethics committee of the hospitals
      (20160920-9). Written informed consents will be signed by the patients or their legally
      authorized representatives. The study was registered in the website of ClinicalTrial.gov .

      Sites and patients Doctors from eight hospitals attended the kick-off meeting held in
      Courtyard Marriott, Hangzhou, March 19th, 2016, and discussed the research protocol and
      details. The amended research protocol was passed according to revised discussion results and
      the agreement of all participating units. The methods of blood pressure measurement and the
      apparatus used are unified. All hospitals will adopt similar non-invasive blood pressure
      monitoring method and unified monitoring frequency to observe whether the blood pressure is
      controlled within the target range in two groups. Likewise, the blood pressure target after
      discharge was maintained at the same levels.

      All patients with AD from the participating hospitals who conform to the following inclusion
      and exclusion criteria will be randomized. Inclusion and exclusion criteria were shown in
      other parts.

      Randomization Blocked randomization was adopted and the intensive and conventional blood
      pressure control treatments were allocated at random in a ratio of 1:1 in blocks of sizes of
      4,6,8, and 10 to 360 subjects. The study is an open label trial. After investigators in each
      participating centers screened the potential patients within 4 hours after acute onset, a
      number from a pre-allocated envelope will be gotten and which denotes which group the patient
      will be allocated to.

      Treatments All the patients were admitted to ICU or general wards at the discretion of
      doctors. Based on the guidelines of aortic management, all patients received analgesic
      therapy and standard control of heart rate and blood pressure treatments. Intravenous esmolol
      was used for continuous control of heart rates. Choice of intravenous antihypertensive agents
      was at the discretion of the in charge physicians. After the stabilization of the situation,
      the intravenous medications were shifted to the oral treatments. The target blood pressure
      for the intensive and conventional groups were <140mmHg and <120mmHg respectively. For most
      patients, they will undergo an endovascular treatment approximate two weeks later.

      Study endpoints The primary outcome is a composite in-hospital adverse outcome, including
      death, permanent paraplegia or semi- paralysis during the hospitalization, and renal failure
      requiring hemodialysis at discharge.

      The secondary outcomes include the mortality in 6-month and 1-year, ICU length of stay, total
      length of hospital stay, postoperative renal injury, and re- intervention.

      Data collection Research coordinators of individual participating hospital will collect the
      required data on the case report form. However, the data was de-named and special security
      code was required to access the data. To facilitate the communications between investigators,
      the case report form was written in Chinese. The primary research institute is responsible
      for collecting and checking the data of all centers; and will contact the co-investigators in
      various centers for checking or revising should they had any question. The primary research
      institute has established an independent study quality control group to implement the
      disposal plan for all unexpected circumstances that may occur.

      Sample size calculation and interim analysis The primary outcome was a composite in-hospital
      adverse outcome, including the death, stroke, permanent paraplegia or semi- paralysis during
      the hospitalization, and renal failure requiring hemodialysis at discharge. Bashir et al
      reported that the incidence of comprehensive nosocomial severe prognostic adverse events of
      ABAD was 45.2%. Assume that the incidence of severe prognosis adverse event in comprehensive
      hospital after intensive blood pressure control could be reduced to 30%, so a total of 322
      subjects enrolled in the study are sufficient to find the difference statistically between
      two groups through the appropriate software calculation under the power of 0.8 and at the
      two-side test with α = 0.05. Considering a dropout rate of 10%, it is proposed to include 360
      cases totally into the study. A formal interim analysis was conducted halfway during study
      enrollment. The overall type I error was controlled using an O'Brien-Fleming spending
      function, with a final significance level of 0.05 for the primary end point.

      Statistical analysis Descriptive data were reported as either mean ± SD, median
      (interquartile range) or number and percentage. With respect to the differences between two
      groups, categorical variables were compared using chi-square analysis. Continuous variables
      were compared using Independent Sample T test for normally distributed data and Mann-Whitney
      U test for non-normally distributed data. For survival analyses, Kaplan-Meier estimates were
      generated to assess differences between groups using the log-rank test, and expressed the
      data as cumulative mortality curves. Statistical analysis was performed by using SPSS 16.0
      (Chicago, Ill, USA) and PASS 11.0. Statistical significance was defined as a P value <0.05.

      Discussion ABAD comprises approximately 30% of all aortic dissection cases. In contrast with
      type A aortic dissection, patients with type B dissection are tend to be older, have higher
      rates of atherosclerosis. Initial goals for acute aortic dissection management are directed
      at control of blood pressure and heart rate, which subsequently limiting propagation of the
      false lumen by controlling aortic shear stress. Whilst medical management has demonstrated an
      in-hospital mortality rate less than 10%, post-discharge the acute type B aortic disease
      continues to evolve eventually resulting in complicated type B disease. Moreover, complicated
      acute type B aortic dissection shows even more striking mortality as high as 30%,
      particularly in the elderly. Poor control of blood pressure was believed to be one of the
      main reasons for the progress of the type B aortic dissection into complications or even the
      laceration extended to the ascending aorta. Dalsart and colleague demonstrated that a
      systolic blood pressure more than 130 mmHg was associated with a bigger aortic enlargement in
      type B aortic dissection (P=0.02) . In another study of 25 years follow-up in 252 patients
      who received repair of acute type A aortic dissection, patients who maintained a systolic
      blood pressure <120 mm Hg had improved freedom from reoperation, compared to those target
      blood pressure 120-140 mm Hg or >140 mm Hg. Hence, most guidelines recommended a reasonable
      initial target for systolic blood pressure is between 100 and 120 mm Hg. However, this target
      is based on the hypothesis that all the end-organs blood supply is not compromised. Data from
      International Registry of Acute Aortic Dissection (IRAD) has shown that approximately one
      quarter of patients presenting with acute type B aortic dissection are followed into
      complicated category, including malperfusion of spinal arteries leading to paresis, and
      paraplegia or malperfusion of visceral arteries leading to abdominal pain. Thus, how to
      balance the decrease of blood pressure to the lowest amount and maintain adequate end-organ
      perfusion is a challenge. Given vast majority patients with type B aortic dissection had a
      history of hypertension, a too lower target of blood pressure may comprise the cerebral
      perfusion or complicated organ perfusion, which consequently caused stroke or other morbidity
      such as ischemic intestinal necrosis. On the other hand, a much strict blood pressure target
      and sometimes constrain on the patients daily activities may aggravate patients' worry, which
      inversely increased increase the blood pressure. Unfortunately, there is no empirical data or
      trials to guide the optimal blood pressure target setting for various patients. Hence, the
      study was designed to bridge the gap.

      In conclusion, the investigators believe that the study will provide new insight into the of
      blood pressure management of patients of acute Type B aortic dissection and subsequently
      improve the outcomes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: composite in-hospital adverse outcome
time frame: From date of randomization until the date of death from any cause，or permanent paraplegia or semi- paralysis during the hospitalization, and renal failure requiring hemodialysis at discharge, whichever came first, assessed up to 3 months
description: including death, permanent paraplegia or semi- paralysis during the hospitalization, and renal failure requiring hemodialysis at discharge
measure: mortality
time frame: 6-month and 1-year after onset of the dissection
description: All cause mortality
measure: ICU length of stay
time frame: From date of ICU admission until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 3 months
measure: re-operation or another endovascular intervention for the same problem
time frame: From date of first intervention until the date of second intervention, assessed up to 12 months
description: any intervention for the same situation such as operation or endovascular intervention
arm group label: Intensive BP control (<120mmHg)
arm group type: Experimental
description: Urapidil Hydrochloride Injection (100-400ug/min) or other antihypertensive agents to decrease the BP to < 120 mm Hg
arm group label: Conventional BP control (120-140mmHg)
arm group type: Active Comparator
description: Urapidil Hydrochloride Injection (100-400ug/min) or other antihypertensive agents to decrease the BP to 120-140 mm Hg
intervention type: Drug
intervention name: Urapidil Hydrochloride Injection
description: Urapidil Hydrochloride Injection or other antihypertensive agents to decrease the BP to the target level.
arm group label: Conventional BP control (120-140mmHg)
arm group label: Intensive BP control (<120mmHg)
other name: Urapidil
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Yun-song Yu, MD
role: Study Director
affiliation: Zhejiang University
last name: Ying-zhi Fang, MD
phone: +86 571 86006987
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sir Run Run Shaw Hospital
investigator full name: Jian-cang Zhou M.D.
investigator title: Principal Investigator
mesh term: Aortic Dissection
mesh term: Hypertension
mesh term: Urapidil
sharing ipd: No