<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/NCT03296189</url>
  </required_header>
  <id_info>
    <org_study_id>AMNCH-GU-2017-2</org_study_id>
    <nct_id>NCT03296189</nct_id>
  </id_info>
  <brief_title>Local Anaesthetic and Steroid in the Ureter</brief_title>
  <acronym>LASTE</acronym>
  <official_title>Intraluminal Ureteric Injection of High Concentration Alkalinised Long-acting Local Anaesthetic and STeroid Post urEteroscopy: A Prospective Double Blinded Randomised Controlled Trial (LASTE Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Adelaide and Meath Hospital, incorporating The National Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Adelaide and Meath Hospital, incorporating The National Children's Hospital</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>
      Précis:&#xD;
&#xD;
      Randomised control trial to evaluate safety and efficacy of intraluminal injection of high&#xD;
      pH-high concentration of a long-acting local anesthetic and long-acting glucocorticoid in the&#xD;
      ureter after ureteroscopy.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      To evaluate a novel method to ameliorate post-ureteroscopy pain in all patients (with and&#xD;
      without stents)&#xD;
&#xD;
      Endpoints:&#xD;
&#xD;
      Primary endpoint: mean visual analog pain scale (VAS) post-operatively starting at 1 hour, 4&#xD;
      hours, 8 hours, 24 hours and 7 days post-procedure (minimum of 3 VAS scores). VAS pain,&#xD;
      ureteral stent symptoms and analgesic requirement will be assessed at different points during&#xD;
      this time period.&#xD;
&#xD;
      Secondary endpoint: Postoperative Nausea/Vomiting (PONV), safety of intraluminal injection of&#xD;
      high concentration alkalinized local anaesthetic solution by comparing adverse events between&#xD;
      placebo and treatment arms. In addition, rehospitalisation rates and postoperative length of&#xD;
      stay will be compared between the three groups.&#xD;
&#xD;
      Population:&#xD;
&#xD;
      150 adult patients undergoing ureteroscopy for ureteric stone disease stratified into&#xD;
      negative ureteroscopy and those treated for a stone with or without stent insertion&#xD;
      postoperatively Number of Sites: Tallaght Hospital Study Duration: 8 months&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Rationale Ureteroscopy is a widely performed procedure in urology. Pain is one of the&#xD;
      commonest complications after ureteroscopy and one of the common reasons for re-admission&#xD;
      after this procedure. Insertion of a stent post-ureteroscopy can cause pain affecting daily&#xD;
      activities in 80% of the patients. Pain post ureteroscopy is multi-factorial and currently&#xD;
      there is no specific method used clinically to treat this. Intraluminal injection of local&#xD;
      anesthetic solution in the ureter has been extensively studied in the animal model with&#xD;
      positive results. Intraluminal injection steroids has also been studied previously and&#xD;
      steroids have also been used in medical expulsive therapy for ureteric stones previously. The&#xD;
      investigators are proposing the use of high concentration alkalinized long-acting local&#xD;
      anaesthetic levo-bupivicaine and long-acting steroid dexamethasone for post-ureteroscopy&#xD;
      pain. It is simple, cheap, safe, easy to perform and widely available.&#xD;
&#xD;
      Background Intraluminal injection of local anesthetics (LA) in the ureter has been studied&#xD;
      previously in animal models. Burdgya et al in 1986, USSR examined effects of LA on guinea pig&#xD;
      ureters . Action potential of ureteric smooth muscle has initial fast component consisting of&#xD;
      repeated gradually decaying spikes and a subsequent slow component i.e plateau. This action&#xD;
      potential is accompanied by a brief contraction. Two opposite effects of LA occur on ureteric&#xD;
      smooth muscle: Low concentrations of procaine, lignocaine and tetracaine (0.1-1 mM) at pH 7.4&#xD;
      increased duration of slow plateau of the evoked action potentials. At higher concentrations&#xD;
      lignocaine (5mM) and tetracaine (0.5mM) caused complete inhibition of evoked action&#xD;
      potentials and phasic contractions. Procaine 5mM predominantly inhibited contractile&#xD;
      responses. High pH (9) significantly increased while low pH (pH 6) decreased the inhibitory&#xD;
      action of procaine and lignocaine. Tetracaine had the most potent inhibitory action on ureter&#xD;
      smooth muscle with the weakest stimulant action while lignocaine had stronger inhibitory&#xD;
      effect on ureter smooth muscle than procaine. Ross et al in 1972 reported intraluminal&#xD;
      injection of 2% lignocaine reduced peristaltic activity in 5 out of 15 ureters in their&#xD;
      patients with no effect in the remaining group.&#xD;
&#xD;
      Andersson and Ulmsten found that local instillation of 4% lignocaine in their patients caused&#xD;
      an initial brief stimulation followed by reduced activity. Tsuchida in 197 studied dog&#xD;
      ureters to report prompt inhibitory effect of 4% lignocaine applied to mucosa invivo with no&#xD;
      effect when applied to adventitia.&#xD;
&#xD;
      Struthers in 1976 in his invivo dog studies found both systemic and intraluminal&#xD;
      administration of lignocaine, procaine and mepivacaine caused only hyperperistalsis and never&#xD;
      inhibition. Sur et al published a study with intravesical injection of ropivacaine before&#xD;
      ureteroscopic surgery demonstrated trends toward decreased pain and voiding symptoms.&#xD;
      Patients received five injections of 2 mL 0.5% ropivacaine around the ureteral orifice or to&#xD;
      the control cohort, who received five injections of 2 mL of 0.9% normal saline in identical&#xD;
      locations. A pilot study suggested that PSD597 (intravesical alkalinized lidocaine) is&#xD;
      effective for treating interstitial cystitis/painful bladder syndrome (IC/PBlS) , providing&#xD;
      short-term amelioration of symptoms in a substantial proportion of patients, with a strong&#xD;
      suggestion that repeating the treatment has a potentially cumulative effect. A randomized&#xD;
      controlled trial comparing injection of non-irritating salt water (placebo), and half an&#xD;
      injection of pH buffered lidocaine before the stent placement in patients undergoing&#xD;
      ureteroscopy is currently being conducted. Till date there is no human study assessing the&#xD;
      efficacy and safety of high concentration alkalinised long-acting LA injection for&#xD;
      post-ureteroscopy pain based on the results of the animal studies outlined above.&#xD;
&#xD;
      The anaesthetic drug chosen for this study is levobupivacaine (Chirocaine™ -): it is S-isomer&#xD;
      of bupivacaine, an amino-amide local anaesthetic widely used in regional anaesthesia, in&#xD;
      postoperative analgesia and in treatment of acute and chronic pain. This drug produces&#xD;
      sensory and motor nerve conduction block, acting on sodium channels of the cell membrane -&#xD;
      sensitive to electric stimulus - but also on potassium and calcium channels. Moreover, it is&#xD;
      remarkable for a rapid onset time and a long duration. In vitro and in vivo pharmacodynamic&#xD;
      studies show that levobupivacaine has the same potency as bupivacaine, though the former is&#xD;
      less likely to cause cardio- and neurotoxicity.&#xD;
&#xD;
      The effect of steroids on ureteric motility has previously been studied in in-vitro sheep&#xD;
      models. Glucocorticoids inhibit the release of phospholipase A2 enzyme which catalyses the&#xD;
      release of arachidonic acid from membrane phospholipids and thereby can have a spasmolytic&#xD;
      action on the ureter by a prostaglandin-inhibitory action. Dexamethasone has shown the most&#xD;
      potent dose dependant effect on the ureteral motility, it blocks ureteral motility in high&#xD;
      concentrations within 24 minutes of instillation. Being a long-acting steroid, its duration&#xD;
      of action in previous studies on nerve blocks and intra-articular injections is demonstrated&#xD;
      at 12 weeks.&#xD;
&#xD;
      Study population: 150 patients undergoing ureteroscopy for ureteric stones:&#xD;
&#xD;
        1. Ureteric stone treatment (including proximal, mid and distal ureteric stones) with or&#xD;
           without JJ stent insertion OR&#xD;
&#xD;
        2. Negative ureteroscopy (no stone found)&#xD;
&#xD;
      Pre and intraop: Obtain informed written consent pre-operatively with a pre-operative pain&#xD;
      score, and rule out any allergies. Standardised uniform anesthetic regimen in all&#xD;
      ureteroscopies.Post-ureteroscopy: drain the renal pelvis&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">November 1, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2019</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>
    <intervention_model_description>Three arm double-blinded prospective randomised controlled trial</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>10 mls of solution will be handed to operating surgeon by the scrub nurse. The nurse will be the only person aware of the solution content and it will be documented discreetly. The operating surgeon, the investigator and the patients will not be aware of the solution used.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Pain</measure>
    <time_frame>at up to 7 days post op</time_frame>
    <description>Visual Analog Pain Scale (VAS) at least 3 different time points post-ureteroscopy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Postoperative Nausea and Vomiting (PONV)</measure>
    <time_frame>at up to 7 days post op</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay post-op</measure>
    <time_frame>at up to 7 days post op</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rehospitalisation rate</measure>
    <time_frame>at up to 7 days post op</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for analgesia</measure>
    <time_frame>at up to 7 days post op</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Pain, Postoperative</condition>
  <condition>Ureter Stone</condition>
  <arm_group>
    <arm_group_label>Local anaesthetic</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Post-ureteroscopy intraluminal injection of alkalinised high concentration levo-bupivicaine in the renal pelvis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Local anaesthetic + steroid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Post-ureteroscopy intraluminal injection of 10 mls alkalinised high concentration levo-bupivicaine with l dexamethasone in the renal pelvis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Post-ureteroscopy intraluminal injection of 10 mls normal saline (placebo) in the renal pelvis</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levobupivacaine</intervention_name>
    <description>intraluminal injection post procedure for pain relief: alkalinised high concentration 10 mls</description>
    <arm_group_label>Local anaesthetic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone Sodium Phosphate</intervention_name>
    <description>intraluminal injection post procedure for pain relief: alkalinised high concentration 10 mls levobupivicaine and 2mls dexamethasone</description>
    <arm_group_label>Local anaesthetic + steroid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>10 mls normal saline</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any patient undergoing ureteroscopy for ureteric stone disease&#xD;
&#xD;
          -  Able to undergo a general anaesthetic&#xD;
&#xD;
          -  At least 18 years old&#xD;
&#xD;
          -  Willing and able to complete patient symptom questionnaires&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Solitary Kidney&#xD;
&#xD;
          -  Renal failure&#xD;
&#xD;
          -  Anatomic bladder or ureteral abnormality&#xD;
&#xD;
          -  Uncorrected coagulopathy&#xD;
&#xD;
          -  Previous cystectomy or urinary diversion&#xD;
&#xD;
          -  Neurogenic bladder&#xD;
&#xD;
          -  Interstitial cystitis&#xD;
&#xD;
          -  Transplanted kidney&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Requires an indwelling catheter&#xD;
&#xD;
          -  Recurrent urinary tract infections&#xD;
&#xD;
          -  Pelvic kidney&#xD;
&#xD;
          -  Requires bilateral treatment/stents&#xD;
&#xD;
          -  Previous bladder or ureteral reconstructive surgery&#xD;
&#xD;
          -  Ureteral perforation during procedure&#xD;
&#xD;
          -  Known sensitivity to lidocaine&#xD;
&#xD;
          -  Febrile at time of randomization or treatment&#xD;
&#xD;
          -  Requires spinal anaesthetic&#xD;
&#xD;
          -  Stenting without stone treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Nikita Bhatt</last_name>
    <phone>00353860609430</phone>
    <email>nikitarb89@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rustom Manecksha</last_name>
    <email>rustom.manecksha@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Adelaide and Meath incorporating National Children's hopsital</name>
      <address>
        <city>Dublin</city>
        <zip>24</zip>
        <country>Ireland</country>
      </address>
    </facility>
    <contact>
      <last_name>Nikita R Bhatt</last_name>
      <phone>00353860609430</phone>
      <email>nikitarb89@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Rustom P Manecksha</last_name>
      <email>rustom.manecksha@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Rustom P Manecksha, MD, FRCSI</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nikita R Bhatt, MRCS MCh</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gerard Fitzpatrick, MB FFARCSI FJFICMI</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <reference>
    <citation>El Harrech Y, Abakka N, El Anzaoui J, Ghoundale O, Touiti D. Ureteral stenting after uncomplicated ureteroscopy for distal ureteral stones: a randomized, controlled trial. Minim Invasive Surg. 2014;2014:892890. doi: 10.1155/2014/892890. Epub 2014 Nov 9.</citation>
    <PMID>25431663</PMID>
  </reference>
  <reference>
    <citation>Burdyga ThV, Magura IS. The effects of local anaesthetics on the electrical and mechanical activity of the guinea-pig ureter. Br J Pharmacol. 1986 Jul;88(3):523-30. doi: 10.1111/j.1476-5381.1986.tb10232.x.</citation>
    <PMID>3742148</PMID>
  </reference>
  <reference>
    <citation>Ross JA EP, Kirkland IS. Ibid. 1972:125.</citation>
  </reference>
  <reference>
    <citation>Andersson KE, Ulmsten U. Effects of spinal anaesthesia, lidocaine, and morphine, on the motility of the human ureter in vivo. Scand J Urol Nephrol. 1975;9(3):236-42. doi: 10.3109/00365597509134219.</citation>
    <PMID>1209180</PMID>
  </reference>
  <reference>
    <citation>Boyarsky ASaS. The Pharmacology of the Urinary Tract. In: Caine M, editor.1984.</citation>
  </reference>
  <reference>
    <citation>Sur RL, Haleblian GE, Cantor DA, Springhart WP, Albala DM, Preminger GM. Efficacy of intravesical ropivacaine injection on urinary symptoms following ureteral stenting: a randomized, controlled study. J Endourol. 2008 Mar;22(3):473-8. doi: 10.1089/end.2007.9847.</citation>
    <PMID>18290733</PMID>
  </reference>
  <reference>
    <citation>Nickel JC, Moldwin R, Lee S, Davis EL, Henry RA, Wyllie MG. Intravesical alkalinized lidocaine (PSD597) offers sustained relief from symptoms of interstitial cystitis and painful bladder syndrome. BJU Int. 2009 Apr;103(7):910-8. doi: 10.1111/j.1464-410X.2008.08162.x. Epub 2008 Nov 13.</citation>
    <PMID>19021619</PMID>
  </reference>
  <reference>
    <citation>The American Heritage® Stedman's Medical Dictionary. http://www.dictionary.com/browse/life-expectancy. Accessed 13/12/16. 2002.</citation>
  </reference>
  <reference>
    <citation>Angelo-Khattar M, Thulesius O, Cherian T. The effect of glucocorticosteroids on in vitro motility of the ureter of the sheep. Br J Pharmacol. 1989 Mar;96(3):527-30. doi: 10.1111/j.1476-5381.1989.tb11849.x.</citation>
    <PMID>2720291</PMID>
  </reference>
  <reference>
    <citation>Manchikanti L, Manchikanti KN, Manchukonda R, Cash KA, Damron KS, Pampati V, McManus CD. Evaluation of lumbar facet joint nerve blocks in the management of chronic low back pain: preliminary report of a randomized, double-blind controlled trial: clinical trial NCT00355914. Pain Physician. 2007 May;10(3):425-40.</citation>
    <PMID>17525777</PMID>
  </reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>January 12, 2018</last_update_submitted>
  <last_update_submitted_qc>January 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Adelaide and Meath Hospital, incorporating The National Children's Hospital</investigator_affiliation>
    <investigator_full_name>Rustom P Manecksha, MD, FRCS (Urol.)</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>ureteroscopy</keyword>
  <keyword>ureteric stent</keyword>
  <keyword>intraluminal</keyword>
  <keyword>local anaesthetic/anesthetic</keyword>
  <keyword>steroid/glucocorticoid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>Levobupivacaine</mesh_term>
    <mesh_term>Dexamethasone 21-phosphate</mesh_term>
    <mesh_term>BB 1101</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03296189
org study id: AMNCH-GU-2017-2
nct id: NCT03296189
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Précis:

      Randomised control trial to evaluate safety and efficacy of intraluminal injection of high
      pH-high concentration of a long-acting local anesthetic and long-acting glucocorticoid in the
      ureter after ureteroscopy.

      Objectives:

      To evaluate a novel method to ameliorate post-ureteroscopy pain in all patients (with and
      without stents)

      Endpoints:

      Primary endpoint: mean visual analog pain scale (VAS) post-operatively starting at 1 hour, 4
      hours, 8 hours, 24 hours and 7 days post-procedure (minimum of 3 VAS scores). VAS pain,
      ureteral stent symptoms and analgesic requirement will be assessed at different points during
      this time period.

      Secondary endpoint: Postoperative Nausea/Vomiting (PONV), safety of intraluminal injection of
      high concentration alkalinized local anaesthetic solution by comparing adverse events between
      placebo and treatment arms. In addition, rehospitalisation rates and postoperative length of
      stay will be compared between the three groups.

      Population:

      150 adult patients undergoing ureteroscopy for ureteric stone disease stratified into
      negative ureteroscopy and those treated for a stone with or without stent insertion
      postoperatively Number of Sites: Tallaght Hospital Study Duration: 8 months
Study Rationale Ureteroscopy is a widely performed procedure in urology. Pain is one of the
      commonest complications after ureteroscopy and one of the common reasons for re-admission
      after this procedure. Insertion of a stent post-ureteroscopy can cause pain affecting daily
      activities in 80% of the patients. Pain post ureteroscopy is multi-factorial and currently
      there is no specific method used clinically to treat this. Intraluminal injection of local
      anesthetic solution in the ureter has been extensively studied in the animal model with
      positive results. Intraluminal injection steroids has also been studied previously and
      steroids have also been used in medical expulsive therapy for ureteric stones previously. The
      investigators are proposing the use of high concentration alkalinized long-acting local
      anaesthetic levo-bupivicaine and long-acting steroid dexamethasone for post-ureteroscopy
      pain. It is simple, cheap, safe, easy to perform and widely available.

      Background Intraluminal injection of local anesthetics (LA) in the ureter has been studied
      previously in animal models. Burdgya et al in 1986, USSR examined effects of LA on guinea pig
      ureters . Action potential of ureteric smooth muscle has initial fast component consisting of
      repeated gradually decaying spikes and a subsequent slow component i.e plateau. This action
      potential is accompanied by a brief contraction. Two opposite effects of LA occur on ureteric
      smooth muscle: Low concentrations of procaine, lignocaine and tetracaine (0.1-1 mM) at pH 7.4
      increased duration of slow plateau of the evoked action potentials. At higher concentrations
      lignocaine (5mM) and tetracaine (0.5mM) caused complete inhibition of evoked action
      potentials and phasic contractions. Procaine 5mM predominantly inhibited contractile
      responses. High pH (9) significantly increased while low pH (pH 6) decreased the inhibitory
      action of procaine and lignocaine. Tetracaine had the most potent inhibitory action on ureter
      smooth muscle with the weakest stimulant action while lignocaine had stronger inhibitory
      effect on ureter smooth muscle than procaine. Ross et al in 1972 reported intraluminal
      injection of 2% lignocaine reduced peristaltic activity in 5 out of 15 ureters in their
      patients with no effect in the remaining group.

      Andersson and Ulmsten found that local instillation of 4% lignocaine in their patients caused
      an initial brief stimulation followed by reduced activity. Tsuchida in 197 studied dog
      ureters to report prompt inhibitory effect of 4% lignocaine applied to mucosa invivo with no
      effect when applied to adventitia.

      Struthers in 1976 in his invivo dog studies found both systemic and intraluminal
      administration of lignocaine, procaine and mepivacaine caused only hyperperistalsis and never
      inhibition. Sur et al published a study with intravesical injection of ropivacaine before
      ureteroscopic surgery demonstrated trends toward decreased pain and voiding symptoms.
      Patients received five injections of 2 mL 0.5% ropivacaine around the ureteral orifice or to
      the control cohort, who received five injections of 2 mL of 0.9% normal saline in identical
      locations. A pilot study suggested that PSD597 (intravesical alkalinized lidocaine) is
      effective for treating interstitial cystitis/painful bladder syndrome (IC/PBlS) , providing
      short-term amelioration of symptoms in a substantial proportion of patients, with a strong
      suggestion that repeating the treatment has a potentially cumulative effect. A randomized
      controlled trial comparing injection of non-irritating salt water (placebo), and half an
      injection of pH buffered lidocaine before the stent placement in patients undergoing
      ureteroscopy is currently being conducted. Till date there is no human study assessing the
      efficacy and safety of high concentration alkalinised long-acting LA injection for
      post-ureteroscopy pain based on the results of the animal studies outlined above.

      The anaesthetic drug chosen for this study is levobupivacaine (Chirocaine™ -): it is S-isomer
      of bupivacaine, an amino-amide local anaesthetic widely used in regional anaesthesia, in
      postoperative analgesia and in treatment of acute and chronic pain. This drug produces
      sensory and motor nerve conduction block, acting on sodium channels of the cell membrane -
      sensitive to electric stimulus - but also on potassium and calcium channels. Moreover, it is
      remarkable for a rapid onset time and a long duration. In vitro and in vivo pharmacodynamic
      studies show that levobupivacaine has the same potency as bupivacaine, though the former is
      less likely to cause cardio- and neurotoxicity.

      The effect of steroids on ureteric motility has previously been studied in in-vitro sheep
      models. Glucocorticoids inhibit the release of phospholipase A2 enzyme which catalyses the
      release of arachidonic acid from membrane phospholipids and thereby can have a spasmolytic
      action on the ureter by a prostaglandin-inhibitory action. Dexamethasone has shown the most
      potent dose dependant effect on the ureteral motility, it blocks ureteral motility in high
      concentrations within 24 minutes of instillation. Being a long-acting steroid, its duration
      of action in previous studies on nerve blocks and intra-articular injections is demonstrated
      at 12 weeks.

      Study population: 150 patients undergoing ureteroscopy for ureteric stones:

        1. Ureteric stone treatment (including proximal, mid and distal ureteric stones) with or
           without JJ stent insertion OR

        2. Negative ureteroscopy (no stone found)

      Pre and intraop: Obtain informed written consent pre-operatively with a pre-operative pain
      score, and rule out any allergies. Standardised uniform anesthetic regimen in all
      ureteroscopies.Post-ureteroscopy: drain the renal pelvis
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Three arm double-blinded prospective randomised controlled trial
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
masking description: 10 mls of solution will be handed to operating surgeon by the scrub nurse. The nurse will be the only person aware of the solution content and it will be documented discreetly. The operating surgeon, the investigator and the patients will not be aware of the solution used.
measure: Pain
time frame: at up to 7 days post op
description: Visual Analog Pain Scale (VAS) at least 3 different time points post-ureteroscopy
measure: Postoperative Nausea and Vomiting (PONV)
time frame: at up to 7 days post op
measure: Length of stay post-op
time frame: at up to 7 days post op
measure: rehospitalisation rate
time frame: at up to 7 days post op
measure: Need for analgesia
time frame: at up to 7 days post op
arm group label: Local anaesthetic
arm group type: Active Comparator
description: Post-ureteroscopy intraluminal injection of alkalinised high concentration levo-bupivicaine in the renal pelvis
arm group label: Local anaesthetic + steroid
arm group type: Active Comparator
description: Post-ureteroscopy intraluminal injection of 10 mls alkalinised high concentration levo-bupivicaine with l dexamethasone in the renal pelvis
arm group label: Placebo
arm group type: Placebo Comparator
description: Post-ureteroscopy intraluminal injection of 10 mls normal saline (placebo) in the renal pelvis
intervention type: Drug
intervention name: Levobupivacaine
description: intraluminal injection post procedure for pain relief: alkalinised high concentration 10 mls
arm group label: Local anaesthetic
intervention type: Drug
intervention name: Dexamethasone Sodium Phosphate
description: intraluminal injection post procedure for pain relief: alkalinised high concentration 10 mls levobupivicaine and 2mls dexamethasone
arm group label: Local anaesthetic + steroid
intervention type: Drug
intervention name: Placebos
description: 10 mls normal saline
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nikita Bhatt
phone: 00353860609430
email: nikitarb89@gmail.com
last name: Rustom Manecksha
email: rustom.manecksha@gmail.com
facility: 
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: Ireland
citation: El Harrech Y, Abakka N, El Anzaoui J, Ghoundale O, Touiti D. Ureteral stenting after uncomplicated ureteroscopy for distal ureteral stones: a randomized, controlled trial. Minim Invasive Surg. 2014;2014:892890. doi: 10.1155/2014/892890. Epub 2014 Nov 9.
PMID: 25431663
citation: Burdyga ThV, Magura IS. The effects of local anaesthetics on the electrical and mechanical activity of the guinea-pig ureter. Br J Pharmacol. 1986 Jul;88(3):523-30. doi: 10.1111/j.1476-5381.1986.tb10232.x.
PMID: 3742148
citation: Ross JA EP, Kirkland IS. Ibid. 1972:125.
citation: Andersson KE, Ulmsten U. Effects of spinal anaesthesia, lidocaine, and morphine, on the motility of the human ureter in vivo. Scand J Urol Nephrol. 1975;9(3):236-42. doi: 10.3109/00365597509134219.
PMID: 1209180
citation: Boyarsky ASaS. The Pharmacology of the Urinary Tract. In: Caine M, editor.1984.
citation: Sur RL, Haleblian GE, Cantor DA, Springhart WP, Albala DM, Preminger GM. Efficacy of intravesical ropivacaine injection on urinary symptoms following ureteral stenting: a randomized, controlled study. J Endourol. 2008 Mar;22(3):473-8. doi: 10.1089/end.2007.9847.
PMID: 18290733
citation: Nickel JC, Moldwin R, Lee S, Davis EL, Henry RA, Wyllie MG. Intravesical alkalinized lidocaine (PSD597) offers sustained relief from symptoms of interstitial cystitis and painful bladder syndrome. BJU Int. 2009 Apr;103(7):910-8. doi: 10.1111/j.1464-410X.2008.08162.x. Epub 2008 Nov 13.
PMID: 19021619
citation: The American Heritage® Stedman's Medical Dictionary. http://www.dictionary.com/browse/life-expectancy. Accessed 13/12/16. 2002.
citation: Angelo-Khattar M, Thulesius O, Cherian T. The effect of glucocorticosteroids on in vitro motility of the ureter of the sheep. Br J Pharmacol. 1989 Mar;96(3):527-30. doi: 10.1111/j.1476-5381.1989.tb11849.x.
PMID: 2720291
citation: Manchikanti L, Manchikanti KN, Manchukonda R, Cash KA, Damron KS, Pampati V, McManus CD. Evaluation of lumbar facet joint nerve blocks in the management of chronic low back pain: preliminary report of a randomized, double-blind controlled trial: clinical trial NCT00355914. Pain Physician. 2007 May;10(3):425-40.
PMID: 17525777
responsible party type: Principal Investigator
investigator affiliation: The Adelaide and Meath Hospital, incorporating The National Children's Hospital
investigator full name: Rustom P Manecksha, MD, FRCS (Urol.)
investigator title: Principal investigator
mesh term: Pain, Postoperative
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: Levobupivacaine
mesh term: Dexamethasone 21-phosphate
mesh term: BB 1101
sharing ipd: Undecided