<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/NCT04461535</url>
  </required_header>
  <id_info>
    <org_study_id>ADOPA study</org_study_id>
    <nct_id>NCT04461535</nct_id>
  </id_info>
  <brief_title>Outcomes of AVS With or Without ACTH Stimulation in PA</brief_title>
  <official_title>Adrenal Venous Sampling With or Without Adrenocorticotropic Hormone Stimulation in Primary Aldosteronism: an Outcome-based Randomized Trial (ADOPA Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chongqing Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chongqing Medical University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To compare the effect of different procedures of AVS(with or without ACTH stimulation) on the&#xD;
      long-term outcomes of patients with PA&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective and randomized study involving patients with primary aldosteronism(PA)&#xD;
      who completed AVS.&#xD;
&#xD;
      All paticipants will be randomized into ACTH-stimulated group(Intervention group) and&#xD;
      ACTH-unstimulated group(Control group) Cannulation was considered successful when the&#xD;
      selectivity index (SI), namely plasma cortisol concentration (PCC) in adrenal vein/PCC in&#xD;
      IVC≥3 with ACTH stimulation or SI≥2 without ACTH stimulation. The ratio of PAC: PCC on the&#xD;
      side with the higher ratio over the contralateral PAC: PCC ratio is defined as the&#xD;
      lateralization index (LI). Lateralization of aldosterone excess was defined as LI≥4&#xD;
      irrespective of ACTH use. Patients with LI between 2 and 4 together with contralateral&#xD;
      suppression (PAC/PCC of non-dominant side &lt; PAC/PCC of IVC) or CT showing a typical adenoma&#xD;
      on the dominant side were also considered to have lateralized disease. Patients with LI &lt; 2&#xD;
      or LI 2-4 without meeting the above criteria were diagnosed as BPA.&#xD;
&#xD;
      In case of technical AVS failure or bilateral PAC/PCC in adrenal venous blood lower than&#xD;
      peripheral blood, if the patient meets one of the following criteria, adrenalectomy was&#xD;
      recommended: 1) unilateral nodule on CT (≥ 1 cm), no observable nodules or hyperplasia on&#xD;
      contralateral adrenal, and PAC ≥ 20 ng/dl, PRC &lt; 5 μIU/ml, K ≤ 3.5mmol/l; 2) unilateral&#xD;
      nodule on CT (≥ 1 cm), no observable nodules or hyperplasia on contralateral adrenal, and the&#xD;
      contralateral index≤0.5 in AVS.&#xD;
&#xD;
      Surgical intervention is recommended for unilateral PA (UPA) whereas bilateral PA (BPA) is&#xD;
      typically treated with oral mineralocorticoid receptor antagonists such as spironolactone.&#xD;
      The aim is to compare the long-term outcomes of patients with PA.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 8, 2020</start_date>
  <completion_date type="Actual">February 20, 2023</completion_date>
  <primary_completion_date type="Actual">February 20, 2023</primary_completion_date>
  <phase>N/A</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>Diagnostic</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Compare the proportion of surgically treated patients with complete biochemical remission in the overall cohort between two groups</measure>
    <time_frame>At 12 months of follow-up.</time_frame>
    <description>Blood was drawn to measure aldosterone, renin and potassium.According to PASO criteria, outcomes of adrenalectomy for unilateral primary aldosteronism were classified into complete, partial, and absent success, for both clinical and biochemical outcomes.The proportion of complete biochemical remission according to PASO consensus criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare the proportion of surgically treated patients who achieved complete clinical remission in the overall cohort between two groups</measure>
    <time_frame>At 12 months of follow-up.</time_frame>
    <description>The proportion of complete clinical remission according to PASO consensus criteria.Clinical outcomes were determined by the blood pressure response to treatment and the number and dosage of antihypertensive medications.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily defined doses (DDD) of antihypertensive agents (including MRA), blood pressure, proportion of patients reaching target blood pressure</measure>
    <time_frame>At 12 months of follow-up.</time_frame>
    <description>Daily defined doses (DDD) of antihypertensive agents (including MRA), blood pressure, proportion of patients reaching target blood pressure in each group irrespective of their treatment after 12 months of follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The rate of successful catheterization of bilateral adrenal veins</measure>
    <time_frame>At baseline.</time_frame>
    <description>Calculate the rate of bilateral successful catheterization.Successful catheterization was defined as SI≥2 without ACTH stimulation or SI≥3 with ACTH stimulation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>At baseline and 12 month of follow-up.</time_frame>
    <description>Record the occurrence of adverse events, including adrenal venous hemorrhage and related adrenal insufficiency, hypertensive urgencies, anaphylactic shock, venous thrombosis, pulmonary embolism, ect.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">228</enrollment>
  <condition>Primary Aldosteronism</condition>
  <arm_group>
    <arm_group_label>AVS with ACTH stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients divided into AVS with ACTH stimulation group need to undergo stimulation with a continuous cosyntropin infusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AVS without ACTH stimulation</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients divided into AVS without ACTH stimulation group take the same procedure of AVS with a continuous saline infusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adrenocorticotropic hormone</intervention_name>
    <description>Patients divided into Intervention group need to undergo stimulation with a continuous cosyntropin infusion (50 μg/h started 30 minutes before sampling during AVS). Right and left adrenal venous blood and corresponding peripheral venous blood should be sampled sequentially.</description>
    <arm_group_label>AVS with ACTH stimulation</arm_group_label>
    <other_name>ACTH</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        1.Inclusion criteria: Patients who meet the following criterion can be included in this&#xD;
        study.&#xD;
&#xD;
          1. Aged between 18-70, male or female, with legal capacity&#xD;
&#xD;
          2. PA diagnosis confirmed by at least one confirmatory test: positive PA screening (ARR≥&#xD;
             2.0 ng·dl-1/IU·l-1) and at least one positive PA confirmatory test (PAC-post CCT ≥11&#xD;
             ng/dl, PAC-post SSIT≥8·0 ng/dl, or if confirmatory tests were in grey zone (i.e, PAC&#xD;
             80-110 pg/ml two hours after administration of 50 mg captopril or PAC 60-80 pg/ml&#xD;
             after the infusion of 2L normal saline), PAC-post FST≥6·0 ng/dl);&#xD;
&#xD;
        2.Exclusion criteria: Patients with one of the following conditions will be excluded in&#xD;
        this study:&#xD;
&#xD;
          1. refusal by the patient to undergo AVS or adrenalectomy;&#xD;
&#xD;
          2. meeting the criteria for bypassing AVS [i.e. younger than 35 years old, with typical&#xD;
             aldosterone-producing adenomas characteristics (plasma aldosterone &gt;30ng/dl, serum&#xD;
             potassium &lt;3·5mmol/l, CT indicated unilateral 1cm low-density adenoma) ;&#xD;
&#xD;
          3. allergic to ACTH or contrast media;&#xD;
&#xD;
          4. pregnant or lactating women;&#xD;
&#xD;
          5. patients with a history of uncontrolled malignant tumor;&#xD;
&#xD;
          6. complicated with Cushing's syndrome [including subclinical Cushing: cortisol after 1mg&#xD;
             dexamethasone suppression test (DST)&gt;138 nmol/l or cortisol after 1mg DST 50-138&#xD;
             nmol/l plus adrenocorticotrophic hormone (ACTH)&lt;10pg/ml;&#xD;
&#xD;
          7. diagnosed with familial hyperaldosteronism;&#xD;
&#xD;
          8. with imaging characteristics suggestive of pheochromocytoma or adrenal cortical&#xD;
             carcinoma;&#xD;
&#xD;
          9. patients unsuitable for surgery, such as those with heart failure (New York Heart&#xD;
             Association (NYHA) class III or IV), severe anemia (Hemoglobin&lt;60g/L), stroke or acute&#xD;
             coronary syndrome within 3 months, severe ascites and cirrhosis, estimated glomerulus&#xD;
             filtration rate&lt;30ml/min/m2;&#xD;
&#xD;
         10. with alcohol or drug abuse and active mental health disorders.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Qifu Li, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>the Chongqing Primary Aldosteronism Study (CONPASS) Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The First Affilated Hospital of Chongqing Medical University</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <zip>400016</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 May;101(5):1889-916. doi: 10.1210/jc.2015-4061. Epub 2016 Mar 2.</citation>
    <PMID>26934393</PMID>
  </results_reference>
  <results_reference>
    <citation>Nishikawa T, Omura M, Satoh F, Shibata H, Takahashi K, Tamura N, Tanabe A; Task Force Committee on Primary Aldosteronism, The Japan Endocrine Society. Guidelines for the diagnosis and treatment of primary aldosteronism--the Japan Endocrine Society 2009. Endocr J. 2011;58(9):711-21. doi: 10.1507/endocrj.ej11-0133. Epub 2011 Aug 9.</citation>
    <PMID>21828936</PMID>
  </results_reference>
  <results_reference>
    <citation>Deinum J, Groenewoud H, van der Wilt GJ, Lenzini L, Rossi GP. Adrenal venous sampling: cosyntropin stimulation or not? Eur J Endocrinol. 2019 Sep;181(3):D15-D26. doi: 10.1530/EJE-18-0844.</citation>
    <PMID>31176302</PMID>
  </results_reference>
  <results_reference>
    <citation>Buffolo F, Monticone S, Williams TA, Rossato D, Burrello J, Tetti M, Veglio F, Mulatero P. Subtype Diagnosis of Primary Aldosteronism: Is Adrenal Vein Sampling Always Necessary? Int J Mol Sci. 2017 Apr 17;18(4):848. doi: 10.3390/ijms18040848.</citation>
    <PMID>28420172</PMID>
  </results_reference>
  <results_reference>
    <citation>Dekkers T, Prejbisz A, Kool LJS, Groenewoud HJMM, Velema M, Spiering W, Kolodziejczyk-Kruk S, Arntz M, Kadziela J, Langenhuijsen JF, Kerstens MN, van den Meiracker AH, van den Born BJ, Sweep FCGJ, Hermus ARMM, Januszewicz A, Ligthart-Naber AF, Makai P, van der Wilt GJ, Lenders JWM, Deinum J; SPARTACUS Investigators. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial. Lancet Diabetes Endocrinol. 2016 Sep;4(9):739-746. doi: 10.1016/S2213-8587(16)30100-0. Epub 2016 Jun 17.</citation>
    <PMID>27325147</PMID>
  </results_reference>
  <results_reference>
    <citation>Williams TA, Lenders JWM, Mulatero P, Burrello J, Rottenkolber M, Adolf C, Satoh F, Amar L, Quinkler M, Deinum J, Beuschlein F, Kitamoto KK, Pham U, Morimoto R, Umakoshi H, Prejbisz A, Kocjan T, Naruse M, Stowasser M, Nishikawa T, Young WF Jr, Gomez-Sanchez CE, Funder JW, Reincke M; Primary Aldosteronism Surgery Outcome (PASO) investigators. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol. 2017 Sep;5(9):689-699. doi: 10.1016/S2213-8587(17)30135-3. Epub 2017 May 30.</citation>
    <PMID>28576687</PMID>
  </results_reference>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>September 3, 2023</last_update_submitted>
  <last_update_submitted_qc>September 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chongqing Medical University</investigator_affiliation>
    <investigator_full_name>Qifu Li</investigator_full_name>
    <investigator_title>Professor.Qifu Li</investigator_title>
  </responsible_party>
  <keyword>primary aldosteronism</keyword>
  <keyword>adrenal venous sampling</keyword>
  <keyword>adrenocorticotropic hormone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperaldosteronism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hormones</mesh_term>
    <mesh_term>Adrenocorticotropic Hormone</mesh_term>
    <mesh_term>Melanocyte-Stimulating Hormones</mesh_term>
    <mesh_term>beta-Endorphin</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/NCT04461535
org study id: ADOPA study
nct id: NCT04461535
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To compare the effect of different procedures of AVS(with or without ACTH stimulation) on the
      long-term outcomes of patients with PA
This is a prospective and randomized study involving patients with primary aldosteronism(PA)
      who completed AVS.

      All paticipants will be randomized into ACTH-stimulated group(Intervention group) and
      ACTH-unstimulated group(Control group) Cannulation was considered successful when the
      selectivity index (SI), namely plasma cortisol concentration (PCC) in adrenal vein/PCC in
      IVC≥3 with ACTH stimulation or SI≥2 without ACTH stimulation. The ratio of PAC: PCC on the
      side with the higher ratio over the contralateral PAC: PCC ratio is defined as the
      lateralization index (LI). Lateralization of aldosterone excess was defined as LI≥4
      irrespective of ACTH use. Patients with LI between 2 and 4 together with contralateral
      suppression (PAC/PCC of non-dominant side < PAC/PCC of IVC) or CT showing a typical adenoma
      on the dominant side were also considered to have lateralized disease. Patients with LI < 2
      or LI 2-4 without meeting the above criteria were diagnosed as BPA.

      In case of technical AVS failure or bilateral PAC/PCC in adrenal venous blood lower than
      peripheral blood, if the patient meets one of the following criteria, adrenalectomy was
      recommended: 1) unilateral nodule on CT (≥ 1 cm), no observable nodules or hyperplasia on
      contralateral adrenal, and PAC ≥ 20 ng/dl, PRC < 5 μIU/ml, K ≤ 3.5mmol/l; 2) unilateral
      nodule on CT (≥ 1 cm), no observable nodules or hyperplasia on contralateral adrenal, and the
      contralateral index≤0.5 in AVS.

      Surgical intervention is recommended for unilateral PA (UPA) whereas bilateral PA (BPA) is
      typically treated with oral mineralocorticoid receptor antagonists such as spironolactone.
      The aim is to compare the long-term outcomes of patients with PA.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Single (Participant)
measure: Compare the proportion of surgically treated patients with complete biochemical remission in the overall cohort between two groups
time frame: At 12 months of follow-up.
description: Blood was drawn to measure aldosterone, renin and potassium.According to PASO criteria, outcomes of adrenalectomy for unilateral primary aldosteronism were classified into complete, partial, and absent success, for both clinical and biochemical outcomes.The proportion of complete biochemical remission according to PASO consensus criteria.
measure: Compare the proportion of surgically treated patients who achieved complete clinical remission in the overall cohort between two groups
time frame: At 12 months of follow-up.
description: The proportion of complete clinical remission according to PASO consensus criteria.Clinical outcomes were determined by the blood pressure response to treatment and the number and dosage of antihypertensive medications.
measure: Daily defined doses (DDD) of antihypertensive agents (including MRA), blood pressure, proportion of patients reaching target blood pressure
time frame: At 12 months of follow-up.
description: Daily defined doses (DDD) of antihypertensive agents (including MRA), blood pressure, proportion of patients reaching target blood pressure in each group irrespective of their treatment after 12 months of follow-up
measure: The rate of successful catheterization of bilateral adrenal veins
time frame: At baseline.
description: Calculate the rate of bilateral successful catheterization.Successful catheterization was defined as SI≥2 without ACTH stimulation or SI≥3 with ACTH stimulation.
measure: Adverse events
time frame: At baseline and 12 month of follow-up.
description: Record the occurrence of adverse events, including adrenal venous hemorrhage and related adrenal insufficiency, hypertensive urgencies, anaphylactic shock, venous thrombosis, pulmonary embolism, ect.
arm group label: AVS with ACTH stimulation
arm group type: Experimental
description: Patients divided into AVS with ACTH stimulation group need to undergo stimulation with a continuous cosyntropin infusion.
arm group label: AVS without ACTH stimulation
arm group type: No Intervention
description: Patients divided into AVS without ACTH stimulation group take the same procedure of AVS with a continuous saline infusion.
intervention type: Drug
intervention name: Adrenocorticotropic hormone
description: Patients divided into Intervention group need to undergo stimulation with a continuous cosyntropin infusion (50 μg/h started 30 minutes before sampling during AVS). Right and left adrenal venous blood and corresponding peripheral venous blood should be sampled sequentially.
arm group label: AVS with ACTH stimulation
other name: ACTH
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Qifu Li, PhD
role: Study Chair
affiliation: the Chongqing Primary Aldosteronism Study (CONPASS) Group
facility: 
country: China
citation: Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 May;101(5):1889-916. doi: 10.1210/jc.2015-4061. Epub 2016 Mar 2.
PMID: 26934393
citation: Nishikawa T, Omura M, Satoh F, Shibata H, Takahashi K, Tamura N, Tanabe A; Task Force Committee on Primary Aldosteronism, The Japan Endocrine Society. Guidelines for the diagnosis and treatment of primary aldosteronism--the Japan Endocrine Society 2009. Endocr J. 2011;58(9):711-21. doi: 10.1507/endocrj.ej11-0133. Epub 2011 Aug 9.
PMID: 21828936
citation: Deinum J, Groenewoud H, van der Wilt GJ, Lenzini L, Rossi GP. Adrenal venous sampling: cosyntropin stimulation or not? Eur J Endocrinol. 2019 Sep;181(3):D15-D26. doi: 10.1530/EJE-18-0844.
PMID: 31176302
citation: Buffolo F, Monticone S, Williams TA, Rossato D, Burrello J, Tetti M, Veglio F, Mulatero P. Subtype Diagnosis of Primary Aldosteronism: Is Adrenal Vein Sampling Always Necessary? Int J Mol Sci. 2017 Apr 17;18(4):848. doi: 10.3390/ijms18040848.
PMID: 28420172
citation: Dekkers T, Prejbisz A, Kool LJS, Groenewoud HJMM, Velema M, Spiering W, Kolodziejczyk-Kruk S, Arntz M, Kadziela J, Langenhuijsen JF, Kerstens MN, van den Meiracker AH, van den Born BJ, Sweep FCGJ, Hermus ARMM, Januszewicz A, Ligthart-Naber AF, Makai P, van der Wilt GJ, Lenders JWM, Deinum J; SPARTACUS Investigators. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial. Lancet Diabetes Endocrinol. 2016 Sep;4(9):739-746. doi: 10.1016/S2213-8587(16)30100-0. Epub 2016 Jun 17.
PMID: 27325147
citation: Williams TA, Lenders JWM, Mulatero P, Burrello J, Rottenkolber M, Adolf C, Satoh F, Amar L, Quinkler M, Deinum J, Beuschlein F, Kitamoto KK, Pham U, Morimoto R, Umakoshi H, Prejbisz A, Kocjan T, Naruse M, Stowasser M, Nishikawa T, Young WF Jr, Gomez-Sanchez CE, Funder JW, Reincke M; Primary Aldosteronism Surgery Outcome (PASO) investigators. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol. 2017 Sep;5(9):689-699. doi: 10.1016/S2213-8587(17)30135-3. Epub 2017 May 30.
PMID: 28576687
responsible party type: Principal Investigator
investigator affiliation: Chongqing Medical University
investigator full name: Qifu Li
investigator title: Professor.Qifu Li
mesh term: Hyperaldosteronism
mesh term: Hormones
mesh term: Adrenocorticotropic Hormone
mesh term: Melanocyte-Stimulating Hormones
mesh term: beta-Endorphin
sharing ipd: No