xml: <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/NCT05977647</url>
    </required_header>
    <id_info>
      <org_study_id>GTZ-MSE-001-23</org_study_id>
      <nct_id>NCT05977647</nct_id>
    </id_info>
    <brief_title>Medical Stone Expulsive Therapy for Acutely Obstructed Ureteric Calculi</brief_title>
    <official_title>Comparison of Silodosin Versus Tamsulosin on Passage of Acutely Obstructing Ureteral Calculi (History of Last 4 Weeks) in Medical Expulsive Therapy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Getz Pharma</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Getz Pharma</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        As a first treatment option for small-size ureteric stones, α-blockers are now being used for&#xD;
        medical expulsive therapy (MET) instead of invasive procedures. There is high evidence of the&#xD;
        therapeutic benefit of α-blockers in the treatment of Distal ureteric stone (DUS); also&#xD;
        endorsed by international guidelines.&#xD;
  &#xD;
        However, limited data is available worldwide, on the effect of silodosin to treat DUS. A&#xD;
        multi-center study is needed to confirm the efficacy and safety of therapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        A kidney stone is a crystal formed inside the kidney. It is one of the commonest conditions&#xD;
        of kidney disease affecting 12% of the world's population. Out of 12% Ureteric stones, around&#xD;
        20% represent cases of urolithiasis, of which 70% are situated in the lower third of the&#xD;
        ureter and are termed as 'Distal Ureteric Stones' (DUS). Kidney stone aggravates the risk of&#xD;
        end-stage kidney disease and increases the risk of multiple complications. including chronic&#xD;
        kidney disease hypertension, diabetes, and cardiovascular diseases. The commonest type of&#xD;
        kidney stone is calcium oxalate, which is present in around 70 to 80% of the total reported&#xD;
        cases of kidney stones.&#xD;
  &#xD;
        There are multiple approaches to the management of ureteric stones, which has evolved over&#xD;
        the last 20 years, specifically due to advancements in technology, use of ureteroscopy and&#xD;
        shockwave lithotripsy (SWL) as minimally invasive treatment options. However, these&#xD;
        interventions are quite expensive and may lead to multiple complications. According to the&#xD;
        complication rate of minimally invasive interventions is 2.5%.&#xD;
  &#xD;
        As a first treatment option for small-size ureteric stones, α-blockers are now being used for&#xD;
        medical expulsive therapy (MET) instead of invasive procedures. As observed through two&#xD;
        meta-analyses there is high evidence of the therapeutic benefit of α-blockers in the&#xD;
        treatment of DUS seen to be 52% and 44% higher than those patients who have not received any&#xD;
        treatment.&#xD;
  &#xD;
        There is an endorsement of the use of a-blockers as a management option for ureteric stones&#xD;
        by the American Urology Association (AUA) and the European Association of Urology. The α1A-&#xD;
        adrenoceptors have proven to play an important effect in intervening contraction of the human&#xD;
        ureter, induced by phenylephrine. Silodosin (selective α1-adrenoceptor blocker) in the human&#xD;
        ureter was found more efficacious than Tamsulosin (1D-adrenoceptor blocker) in&#xD;
        non-adrenaline-induced contractions.&#xD;
  &#xD;
        However, limited data is available worldwide, on the effect of silodosin to treat DUS. To the&#xD;
        best of our knowledge, there has been no study done on the use of silodosin as MET for DUS in&#xD;
        the context of Pakistan. Therefore, this study will be able to provide meaningful data to&#xD;
        find the efficacy and safety of silodosin in comparison to Tamsulosin as MET in ureteric&#xD;
        stone.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2024</primary_completion_date>
    <phase>Phase 4</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>
      <intervention_model_description>Participants will be randomized into two groups.&#xD;
  A permuted block randomization technique will be used&#xD;
  A block represents a separate center/site of enrollment.&#xD;
  There will be 19 recruitment centers&#xD;
  Each center will enroll total 20-25 subjects</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>% of stone expulsion</measure>
      <time_frame>4 weeks</time_frame>
      <description>The primary outcome measure will be the passage of stone expulsion self-reported definitive passage of calculus or the first day of pain-free to 48 hours period with calculus absent of X - ray KUB.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Time in days to stone expulsion</measure>
      <time_frame>4 weeks</time_frame>
      <description>Time in days to stone expulsion: Self-reported definitive passage of calculus or the first day of pain-free to 48 hours period with calculus absent of X - ray.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Frequency of pain reported by patients</measure>
      <time_frame>4 weeks</time_frame>
      <description>Patient will mark the number of episodes of pain in 24 hours on daily basis in patient dairy..</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in intensity of pain</measure>
      <time_frame>4 weeks</time_frame>
      <description>Patient dairy will be provided to all the patients. Which will have pain log scale. They will self-report the intensity of pain (highest intensity) in 24 hours on daily basis. The pain scale ranges are mentioned below.&#xD;
  0 means no pain&#xD;
  1 to 2 means mild pain&#xD;
  2 to 4 means moderate pain&#xD;
  4 to 6 means severe pain&#xD;
  6 to 8 means very severe pain&#xD;
  8 to 10 means worst pain ever</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Usage of analgesics</measure>
      <time_frame>4 weeks</time_frame>
      <description>The subject will be given a standardized pain medication (diclofenac sodium) prescription at their initial visit and will be asked to keep track of how much pain medication they used each day in patient's dairy. This information will be collected at every week on follow up visits.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Frequency of ER visits</measure>
      <time_frame>4 weeks</time_frame>
      <description>Patient will report if he/she had visited ER in last 24 hours on daily basis in patient's dairy along with the medication prescribed in ER.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Frequency of adverse events (Postural hypotension, retrograde ejaculation, etc.)</measure>
      <time_frame>4 weeks</time_frame>
      <description>Patient will be briefed about the known adverse events of study drugs. If any side effects is observed by the patient will be reported in patient dairy.&#xD;
  If any unknown side effects happen that will also be reported in patient diary.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">240</enrollment>
    <condition>Ureteric Stone of Lower Third of Ureter</condition>
    <arm_group>
      <arm_group_label>Tamsulosin</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients with lower ureteric stone will be randomized through permuted block randomization equally into two group. 120 patients will be on tamsulosin 0.4 mg once daily, therapy will be given for a maximum of 4 weeks.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Silodosin</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients with lower ureteric stone will be randomized through permuted block randomization equally into two group. 120 patients will be on Silodosin 8 mg once daily. Therapy will be given for a maximum of 4 weeks.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tamsulosin Oral Capsule</intervention_name>
      <description>Patient will be enrolled in one of study arm through randomization.</description>
      <arm_group_label>Silodosin</arm_group_label>
      <arm_group_label>Tamsulosin</arm_group_label>
      <other_name>silodosin Oral Capsule</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adults male and female aged 18 to 70 years&#xD;
  &#xD;
            -  Patients who give informed consent&#xD;
  &#xD;
            -  Stone located in the distal 1/3rd of ureter (Single, unilateral and radiopaque&#xD;
               ureteral calculus 5 to 10 mm visible on the CT-KUB± X-ray KUB within the ureter&#xD;
  &#xD;
            -  Serum creatinine level within the normal range (adult men, 0.74 to 1.35 mg/dL &amp; 0.59&#xD;
               to 1.04 mg/dL)&#xD;
  &#xD;
            -  Ability to tolerate oral fluids and oral pain medication&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients already taking an alpha-adrenergic antagonist medication for 4 weeks&#xD;
  &#xD;
            -  Evidence of any other renal stone simultaneously present or at any location&#xD;
  &#xD;
            -  Hydronephrosis Grade 3 (Moderate) &amp; Grade 4 (Severe) Patients with eGFR &lt;60&#xD;
               ml/min/1.73m2&#xD;
  &#xD;
            -  Signs of infection including temperature &gt;38ºC or Urinalysis with any of the&#xD;
               following: Positive Leukocyte Esterase, Positive Nitrates, or White Blood Cell Count&#xD;
               &gt;5/hfp in the setting of a positive urine culture (defined as a single isolated&#xD;
               bacterial species population of &gt;100,000 CFU)&#xD;
  &#xD;
            -  Patients with chronic pain already undergoing treatment with narcotic medications or&#xD;
               drug abusers&#xD;
  &#xD;
            -  Pregnant or lactating women&#xD;
  &#xD;
            -  Patient suffering from urinary tract infection, ureteral surgery, and existing DJ&#xD;
               stents.&#xD;
  &#xD;
            -  Clinical jaundice&#xD;
  &#xD;
            -  Any forms of anatomical obstructions in the urinary tract&#xD;
  &#xD;
            -  The previously suffering from postural hypotension&#xD;
  &#xD;
            -  Any other disease jeopardizing participation in trial and could lead to increase&#xD;
               patient health risks&#xD;
  &#xD;
            -  History of allergic reactions with the study drugs (Silodosin or Tamsulosin)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Dr. Mahaveer Maheshwari, MBBS</last_name>
      <phone>+923202521918</phone>
      <email>mahaveer.maheshwari@getzpharma.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Dr. Hussain Baqar Abidi, MBBS</last_name>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 7, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Ureteral Calculi</mesh_term>
      <mesh_term>Ureterolithiasis</mesh_term>
      <mesh_term>Calculi</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tamsulosin</mesh_term>
      <mesh_term>Silodosin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05977647
  org study id: GTZ-MSE-001-23
  nct id: NCT05977647
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  As a first treatment option for small-size ureteric stones, α-blockers are now being used for
        medical expulsive therapy (MET) instead of invasive procedures. There is high evidence of the
        therapeutic benefit of α-blockers in the treatment of Distal ureteric stone (DUS); also
        endorsed by international guidelines.
  
        However, limited data is available worldwide, on the effect of silodosin to treat DUS. A
        multi-center study is needed to confirm the efficacy and safety of therapy.
  A kidney stone is a crystal formed inside the kidney. It is one of the commonest conditions
        of kidney disease affecting 12% of the world's population. Out of 12% Ureteric stones, around
        20% represent cases of urolithiasis, of which 70% are situated in the lower third of the
        ureter and are termed as 'Distal Ureteric Stones' (DUS). Kidney stone aggravates the risk of
        end-stage kidney disease and increases the risk of multiple complications. including chronic
        kidney disease hypertension, diabetes, and cardiovascular diseases. The commonest type of
        kidney stone is calcium oxalate, which is present in around 70 to 80% of the total reported
        cases of kidney stones.
  
        There are multiple approaches to the management of ureteric stones, which has evolved over
        the last 20 years, specifically due to advancements in technology, use of ureteroscopy and
        shockwave lithotripsy (SWL) as minimally invasive treatment options. However, these
        interventions are quite expensive and may lead to multiple complications. According to the
        complication rate of minimally invasive interventions is 2.5%.
  
        As a first treatment option for small-size ureteric stones, α-blockers are now being used for
        medical expulsive therapy (MET) instead of invasive procedures. As observed through two
        meta-analyses there is high evidence of the therapeutic benefit of α-blockers in the
        treatment of DUS seen to be 52% and 44% higher than those patients who have not received any
        treatment.
  
        There is an endorsement of the use of a-blockers as a management option for ureteric stones
        by the American Urology Association (AUA) and the European Association of Urology. The α1A-
        adrenoceptors have proven to play an important effect in intervening contraction of the human
        ureter, induced by phenylephrine. Silodosin (selective α1-adrenoceptor blocker) in the human
        ureter was found more efficacious than Tamsulosin (1D-adrenoceptor blocker) in
        non-adrenaline-induced contractions.
  
        However, limited data is available worldwide, on the effect of silodosin to treat DUS. To the
        best of our knowledge, there has been no study done on the use of silodosin as MET for DUS in
        the context of Pakistan. Therefore, this study will be able to provide meaningful data to
        find the efficacy and safety of silodosin in comparison to Tamsulosin as MET in ureteric
        stone.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Participants will be randomized into two groups.
  A permuted block randomization technique will be used
  A block represents a separate center/site of enrollment.
  There will be 19 recruitment centers
  Each center will enroll total 20-25 subjects
  primary purpose: Treatment
  masking: None (Open Label)
  measure: % of stone expulsion
  time frame: 4 weeks
  description: The primary outcome measure will be the passage of stone expulsion self-reported definitive passage of calculus or the first day of pain-free to 48 hours period with calculus absent of X - ray KUB.
  measure: Time in days to stone expulsion
  time frame: 4 weeks
  description: Time in days to stone expulsion: Self-reported definitive passage of calculus or the first day of pain-free to 48 hours period with calculus absent of X - ray.
  measure: Frequency of pain reported by patients
  time frame: 4 weeks
  description: Patient will mark the number of episodes of pain in 24 hours on daily basis in patient dairy..
  measure: Change in intensity of pain
  time frame: 4 weeks
  description: Patient dairy will be provided to all the patients. Which will have pain log scale. They will self-report the intensity of pain (highest intensity) in 24 hours on daily basis. The pain scale ranges are mentioned below.
  0 means no pain
  1 to 2 means mild pain
  2 to 4 means moderate pain
  4 to 6 means severe pain
  6 to 8 means very severe pain
  8 to 10 means worst pain ever
  measure: Usage of analgesics
  time frame: 4 weeks
  description: The subject will be given a standardized pain medication (diclofenac sodium) prescription at their initial visit and will be asked to keep track of how much pain medication they used each day in patient's dairy. This information will be collected at every week on follow up visits.
  measure: Frequency of ER visits
  time frame: 4 weeks
  description: Patient will report if he/she had visited ER in last 24 hours on daily basis in patient's dairy along with the medication prescribed in ER.
  measure: Frequency of adverse events (Postural hypotension, retrograde ejaculation, etc.)
  time frame: 4 weeks
  description: Patient will be briefed about the known adverse events of study drugs. If any side effects is observed by the patient will be reported in patient dairy.
  If any unknown side effects happen that will also be reported in patient diary.
  arm group label: Tamsulosin
  arm group type: Active Comparator
  description: Patients with lower ureteric stone will be randomized through permuted block randomization equally into two group. 120 patients will be on tamsulosin 0.4 mg once daily, therapy will be given for a maximum of 4 weeks.
  arm group label: Silodosin
  arm group type: Active Comparator
  description: Patients with lower ureteric stone will be randomized through permuted block randomization equally into two group. 120 patients will be on Silodosin 8 mg once daily. Therapy will be given for a maximum of 4 weeks.
  intervention type: Drug
  intervention name: Tamsulosin Oral Capsule
  description: Patient will be enrolled in one of study arm through randomization.
  arm group label: Silodosin
  arm group label: Tamsulosin
  other name: silodosin Oral Capsule
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Dr. Mahaveer Maheshwari, MBBS
  phone: +923202521918
  email: mahaveer.maheshwari@getzpharma.com
  last name: Dr. Hussain Baqar Abidi, MBBS
  responsible party type: Sponsor
  mesh term: Ureteral Calculi
  mesh term: Ureterolithiasis
  mesh term: Calculi
  mesh term: Tamsulosin
  mesh term: Silodosin
  sharing ipd: No