<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/NCT03037892</url>
  </required_header>
  <id_info>
    <org_study_id>KHUH/Research/No.89/2015</org_study_id>
    <nct_id>NCT03037892</nct_id>
  </id_info>
  <brief_title>Comparison of Remifentanil as a Sole Agent or in Combination With Midazolam Versus Fentanyl/Midazolam During Sedation for Colonoscopy</brief_title>
  <official_title>A Prospective Randomized Comparative Study to Evaluate the Use of Remifentanil as a Sole Agent or in Combination With Midazolam Versus Fentanyl/Midazolam During Sedation for Colonoscopy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King Hamad University Hospital, Bahrain</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>King Hamad University Hospital, Bahrain</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Colonoscopy is one of the most commonly performed outpatient procedure for diagnosis and&#xD;
      treatment of lower gastrointestinal tract disorders. It has been largely accepted as an&#xD;
      effective tool for colorectal cancer(CRC) screening, given its ability to detect and remove&#xD;
      identified polyps. Increased colonoscopy utilization is associated with the observed decline&#xD;
      in the incidence of CRC and its diagnosis at earlier stages. Diagnostic and therapeutic&#xD;
      colonoscopy can successfully be performed using moderate sedation in the ambulatory setting.&#xD;
      Techniques of sedation must guarantee the comfort and safety of patients, and at the same&#xD;
      time allow a rapid turnover of patients.. An anaesthetic agent with rapid onset and offset of&#xD;
      action, and convenient titration of anaesthetic/analgesic depth as well as rapid recovery to&#xD;
      enable discharge from the endoscopy unit as soon as possible would be ideal as most such&#xD;
      procedures are performed in the Non-Operating Room Anaesthesia(NORA) settings.&#xD;
&#xD;
      There is recent interest in the use of Remifentanil, in endoscopic units as it might have&#xD;
      advantages over other drugs because of its profound analgesic effects, rapid onset and offset&#xD;
      time and rapid titration to the individual patient's requirements and intermittent pain&#xD;
      during colonoscopy.&#xD;
&#xD;
      The aim of this randomized study is to test the hypothesis that a colonoscopy of good quality&#xD;
      in terms of pain relief, patient comfort and discharge times with less cardiorespiratory side&#xD;
      effects can be performed using Remifentanil as a sole agent as compared with the standard&#xD;
      midazolam/fentanyl protocol. The second group combining Remifentanil with Midazolam is taken&#xD;
      to evaluate if there is any advantage of adding an anxiolytic amnesic drug as used in the&#xD;
      standard Midazolam/Fentanyl Protocol.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Prospective Randomized Comparative Study to Evaluate the Use of Remifentanil as a Sole&#xD;
      Agent or in Combination with Midazolam Versus Fentanyl/Midazolam during Sedation for&#xD;
      Colonoscopy.&#xD;
&#xD;
      Background:&#xD;
&#xD;
      Audits of patient experiences and studies on quality improvement for colonoscopy have shown&#xD;
      that increased sedation administration results in long-lasting improvement of colonoscopy&#xD;
      quality indicators. However deep sedation in NORA ambulatory settings has been associated&#xD;
      with increased sedation associated risks and raises costs for healthcare providers. Sedation&#xD;
      may delay discharge of patients or cause discharge of patients with early cognitive&#xD;
      impairment that contraindicate complex activities of daily living, The search is still on for&#xD;
      an ideal drug that produces optimal operating conditions with minimum postoperative cognitive&#xD;
      impairment.&#xD;
&#xD;
      Remifentanil is an ultrashort, very potent narcotic, which is eliminated by plasma and tissue&#xD;
      esterases. There is recent interest in the use of Remifentanil in endoscopic units as it&#xD;
      might have advantages over other drugs because of its profound analgesic effects, rapid onset&#xD;
      and offset time and rapid titration to the individual patient's requirements and intermittent&#xD;
      pain during colonoscopy. There are a few studies which suggest that the&#xD;
      analgosedation(intense pain relief without loss of consciousness) achievable with&#xD;
      remifentanil is a valid alternative to the present sedo-analgesia techniques used for&#xD;
      colonoscopic sedation.&#xD;
&#xD;
      Ackcaboy ZN conducted a prospective randomized trial to test the hypothesis that continuous&#xD;
      infusion of low dose remifentanil (0.05mcg/kg/min) continuous and bolus injection - in&#xD;
      combination with 2 mg of midazolam, can provide effective analgesia, sedation, amnesia,&#xD;
      patient comfort and stable recovery profile without respiratory depression when compared with&#xD;
      Propofol infusion during colonoscopy.&#xD;
&#xD;
      Following Moerman's hypothesis: &quot;If pain is the crucial point, why do we need sedation?&quot;, the&#xD;
      use of remifentanil as a sole agent for colonoscopy, has been investigated and compared with&#xD;
      the sedative scheme of midazolam plus pethidine. Remifentanil was found to provide sufficient&#xD;
      pain relief with better hemodynamic stability, less respiratory depression, and significantly&#xD;
      faster recovery and hospital discharge than moderate sedation with midazolam and pethidine.&#xD;
      Midazolam-Fentanyl and Midazolam-Remifentanyl techniques has been compared for Endoscopic&#xD;
      Retrograde Cholangio- Pancreatography another painful endoscopic procedure and there were&#xD;
      definite advantages seen in the midazolam-remifentanil group in level of sedation and patient&#xD;
      satisfaction. However, remifentanil use is not widespread and is being used only by&#xD;
      anaesthesiologists.&#xD;
&#xD;
      There is scope to conduct further studies to ascertain if there is an actual real benefit of&#xD;
      using remifentanil as a sole agent or in combination with midazolam, over the standard&#xD;
      technique of midazolam/fentanyl used in endoscopy units.&#xD;
&#xD;
      This Controlled Randomized Clinical Study is planned to evaluate whether Remifentanil by&#xD;
      itself as a sole agent or in combination with Midazolam provides a safe and effective&#xD;
      sedation for colonoscopy as compared to the present technique of midazolam and fentanyl being&#xD;
      used by most endoscopists.&#xD;
&#xD;
      1. Statement of the problem Colonoscopy is a proven method for bowel cancer screening and is&#xD;
      often experienced as a painful procedure. They are the most frequently performed endoscopic&#xD;
      procedures. However motivating patients to participate in colonoscopy screening continues to&#xD;
      be a challenge as it is associated with considerable anxiety and pain. Additionally patients&#xD;
      complain of disruption of normal activities by bowel preparations and hangover effects from&#xD;
      sedation and need for an escort after procedure. The sedation protocol are followed by the&#xD;
      endoscopists' themselves with a nurse who is monitoring the case. Rescue from extreme&#xD;
      sedation or agitation is not uncommon. Ideal sedation should be potent and easily titrated ,&#xD;
      be adequate and safe for the painful procedure yet have a quick recovery for an early&#xD;
      discharge as these procedures are usually done in an ambulatory setting.&#xD;
&#xD;
      Remifentanyl is a relatively new drug which has been used in endoscopic suites with some&#xD;
      advantage. There is scope to conduct further studies to ascertain if there is an actual real&#xD;
      benefit of using remifentanil as a sole agent or in combination with midazolam, over the&#xD;
      standard technique of midazolam/fentanyl..&#xD;
&#xD;
      Significance of the problem&#xD;
&#xD;
      Colonoscopy is one of the most commonly performed outpatient procedure for diagnosis and&#xD;
      treatment of lower gastrointestinal tract disorders, usually performed under moderate&#xD;
      sedation in the ambulatory setting. As pain and vasovagal reactions are common during the&#xD;
      procedure, administration of sedation and analgesia is imperative. Techniques of sedation&#xD;
      must guarantee the comfort and safety of patients, and at the same time allow a rapid&#xD;
      turnover of patients. An anaesthetic agent with rapid onset and offset of action, and&#xD;
      convenient titration of anaesthetic/analgesic depth as well as rapid recovery to enable&#xD;
      discharge from the endoscopy unit as soon as possible would be ideal.&#xD;
&#xD;
      There is recent interest in the use of Remifentanil in endoscopic units as it might have&#xD;
      advantages over other drugs because of its profound analgesic effects, rapid onset and offset&#xD;
      time and rapid titration to the individual patient's requirements and intermittent pain&#xD;
      during colonoscopy. Remifentanil was found to provide sufficient pain relief with better&#xD;
      hemodynamic stability, less respiratory depression, and significantly faster recovery and&#xD;
      hospital discharge than moderate sedation in a few preliminary studies.&#xD;
&#xD;
      Objectives of the study:&#xD;
&#xD;
      General objective:&#xD;
&#xD;
      The study plans to study whether Remifentanil by itself as a sole agent or in combination&#xD;
      with Midazolam provides a safe and effective sedation for colonoscopy as compared to the&#xD;
      present technique of midazolam and fentanyl being used by the endoscopists.&#xD;
&#xD;
      Specific objective:&#xD;
&#xD;
        -  Whether remifentanyl as a sole agent was effective and safe for Colonoscopies, or if&#xD;
           combined with midazolam offered any advantages over the only remifentanyl or standard&#xD;
           midazolam fentanyl technique.&#xD;
&#xD;
        -  Effectiveness will be judged by the number of patients who complained of pain during&#xD;
           procedure, number of patients who became uncooperative during the technique and had to&#xD;
           be given Propofol to convert it into a general anaesthetic.&#xD;
&#xD;
        -  Safety will be judged by any significant haemodynamic or respiratory changes and changes&#xD;
           in sedation level in the various study groups.&#xD;
&#xD;
        -  Advantages in reduced recovery time will be noted from the time to full recovery after&#xD;
           sedation procedure.&#xD;
&#xD;
        -  Patient and Endoscopist's satisfaction score will be recorded to see any differences in&#xD;
           the three groups.&#xD;
&#xD;
      Method:&#xD;
&#xD;
      Following an Ethics Committee approval, 90 patients who are undergoing colonoscopy under&#xD;
      moderate sedation in an ambulatory setting at Awali Hospital will be included in the study&#xD;
      who satisfy the inclusion/exclusion criteria. Informed Consent will be taken preoperatively&#xD;
      and they will be randomly allocated in to three groups as follows:&#xD;
&#xD;
      Group 1 - Patients will receive Midazolam and Fentanyl.&#xD;
&#xD;
      Group 2 - Patients will receive Midazolam and Remifentanil&#xD;
&#xD;
      Group 3 - Patients will receive Remifentanil as a sole agent&#xD;
&#xD;
      Study subjects: Inclusion and exclusion criteria of the study subjects.&#xD;
&#xD;
      Design: Prospective, randomized controlled clinical trial&#xD;
&#xD;
      Sample size: 90 patients will be selected for the study randomly dividing them into the three&#xD;
      groups of 30 each.&#xD;
&#xD;
      Sampling technique: All patients due for colonoscopy under moderate sedation who satisfy the&#xD;
      inclusion and exclusion criteria and who agree to be part of the study group by an informed&#xD;
      consent will be randomly divided into the three groups of 30 each.&#xD;
&#xD;
      Randomization will be done by making identical folded slips of the three groups and by&#xD;
      randomly picking up a slip preoperatively on the morning of procedure for each patient.&#xD;
&#xD;
      Timeframe of the study. The study will be done prospectively once approved by the Ethics&#xD;
      Committee and registered as a Prospective Clinical Trial in the Registry&#xD;
&#xD;
      Data Collection methods, instruments used and measurements: Describe the instruments to be&#xD;
      used for data collection (questionnaire, observation recording form, etc.)&#xD;
&#xD;
      Study Protocol:&#xD;
&#xD;
      Patients undergoing elective colonoscopy who satisfy the inclusion criteria will be randomly&#xD;
      allocated to the 3 groups after taking an informed consent. All colonoscopies will be&#xD;
      performed by two Endoscopists of Awali Hospital who seem to work in a very similar manner for&#xD;
      colonic endoscopy.&#xD;
&#xD;
      On arrival to the endoscopy room an IV access will be established. Supplemental oxygen 3&#xD;
      L/min will be given through both the nostrils and mouth by a specially designed mask which&#xD;
      can monitor the end tidal CO2 level. The basal values of noninvasive blood pressure (NIBP),&#xD;
      peripheral oxygen saturation (SpO2), heart rate (HR), respiratory rate (RR) and end-tidal CO2&#xD;
      level (ETCO2) will be noted.&#xD;
&#xD;
      Two minutes before the colonoscopy procedure, a bolus of midazolam 0.03mg/Kg and&#xD;
      1.5microgram/Kg fentanyl will be given intravenously over 60 sec in group 1. 0.5 mg of&#xD;
      midazolam intravenously can be given every two minutes till the patient is sufficiently&#xD;
      sedated (sleeping but arousable on calling). The colonoscopy can start at this end point.&#xD;
      Increments of 0.5mcg/Kg of fentanyl will be given if patient complains of pain, which can be&#xD;
      repeated every 5 minutes if there is persistent pain. The patient in group 2 Target&#xD;
      controlled infusion of Remifentanil to 3.0 ng/ml will be started 2 minutes before procedure.&#xD;
      The patient will then be given same doses of midazolam in 0.5 mg increments till sedated&#xD;
      sufficiently (sleeping but arousable on verbal command). During Colonoscopy the dose of&#xD;
      Remifentanil could be increased by 0.5ng/ml if patient complained of pain upto 4.0ng/ml. The&#xD;
      group 3 patient will receive only Remifentanil in the same doses as given in group 2. During&#xD;
      the procedure if the pain is excessive and persistent in spite of increasing the respective&#xD;
      doses as prescribed in each group, or causing loss of cooperation of patient and interfering&#xD;
      in the performance of procedure, the patients will be given sleep dose of Inj Propofol and&#xD;
      further anaesthesia care as required will be provided for same.&#xD;
&#xD;
      The Haemodynamic Parameters(NIBP,HR), RR, SPO2, Sedation Scare (Ramsay) and ETCO2 will be&#xD;
      measured 1 and 3 min after the drug dose then every 5 min till end of procedure. After&#xD;
      procedure the patients will be shifted to recovery and the same parameters will continue to&#xD;
      be measured every 5 min until discharge from the 30 min stay in the recovery room. Pain&#xD;
      Scoring will be done by a Visual Analog Pain Score (VAS) (0- minimum to 100mm- Maximum pain)&#xD;
      just after passing the scope, during the scope, just after the completion of colonoscopy and&#xD;
      at the discharge from the recovery unit.&#xD;
&#xD;
      Total amount of drug consumed, duration of colonoscopy, incidence of adverse effects&#xD;
      (desaturation &lt;94% on Pulseoximetry, Hypoventilation (RR&lt;8/min or apneic episode, hypotension&#xD;
      (SBP&lt;90mm Hg), nausea vomiting or pruritis will be recorded.&#xD;
&#xD;
      Patient satisfaction will be noted at the time of discharge from ward&#xD;
&#xD;
      Primary Outcome Measures:&#xD;
&#xD;
      • The Recovery Time The patient will be considered recovered if and when they achieve an&#xD;
      Aldrete score of 10. Aldrete scoring will be done every 5 minutes after completing&#xD;
      colonoscopy up to 30 min or till achievement of a 10/10 Aldrete Score.&#xD;
&#xD;
      Aldrete score&#xD;
&#xD;
        -  Respiration: Able to take deep breath and cough = 2, Dyspnea/shallow breathing = 1,&#xD;
           Apnea = 0&#xD;
&#xD;
        -  O2 saturation: Maintains &gt; 92% on room air =2, Needs O2 inhalation to maintain O2&#xD;
           saturation &gt; 90% =1 , O2 saturation &lt; 90% even with supplemental oxygen =0&#xD;
&#xD;
        -  Consciousness: Fully awake= 2, Arousable on calling = 1, Not responding = 0&#xD;
&#xD;
        -  Circulation: BP +/- 20 mm Hg preop =2, BP +/- 20-50 mm Hg preop =1, BP +/- 50 mm Hg&#xD;
           preop =0&#xD;
&#xD;
        -  Activity: Able to move 4 extremities = 2, Able to move 2 extremities = 1, Able to move 0&#xD;
           extremities 0&#xD;
&#xD;
        -  Participants Assumed to Feel Frequent Pain, during and after colonoscopy. • Patients&#xD;
           sound &quot;Ah&quot; at feeling pain during colonoscopy would be taken as a measure: if a patients&#xD;
           sounds &quot;Ah&quot; &gt; 6 times, the patient was assumed to feel frequent pain. Will be scored as&#xD;
           0 no pain ,1if he complains of pain or 2 if he says Ah or complains of pain frequently,&#xD;
           that is, more than 6 times.&#xD;
&#xD;
        -  Patient's Distress Score every 5 min till the end of colonoscopy. Patients' distress as&#xD;
           minimal, mild moderate or severe distress.&#xD;
&#xD;
        -  Number of patients in each group who had to receive propofol due to loss of cooperation&#xD;
&#xD;
      Secondary Outcome Measures:&#xD;
&#xD;
        -  Endoscopist Satisfaction. Time Frame: 5 min after the colonoscopy. Endoscopist's&#xD;
           satisfaction after colonoscopy in visual analogue scale 100 mm&#xD;
&#xD;
        -  Incidence of Patient's Recall. Tested after colonoscopy before discharge from the&#xD;
           hospital. The numbers of patients who recalled instructions and explanations given&#xD;
           during colonoscopy will be noted and if there was any unpleasantness related to the&#xD;
           recall or awareness.&#xD;
&#xD;
        -  Patient satisfaction. Will be tested on a numerical scale from 0 (not satisfied at all)&#xD;
           to 10 (fully satisfied) at the time of discharge from the hospital.&#xD;
&#xD;
        -  Side Effects noted in each group for example excessive sedation, nausea, vomiting,&#xD;
           pruritis, respiratory depression or apnoea.&#xD;
&#xD;
      The data will be statistically analyzed, to arrive at a conclusion on whether remifentanyl as&#xD;
      a sole agent was effective for Colonoscopies, or if combined with midazolam offered any&#xD;
      advantages over the only remifentanyl or standard midazolam fentanyl technique.&#xD;
&#xD;
      Implications of the study results to population health and health system policy in Awali&#xD;
      Hospital and Bahrain:&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2015</start_date>
  <completion_date type="Actual">May 2018</completion_date>
  <primary_completion_date type="Actual">May 2018</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>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Recovery Time</measure>
    <time_frame>30 min</time_frame>
    <description>Every 5 minutes till a score of 10/10 achieved on Aldrete Score</description>
  </primary_outcome>
  <primary_outcome>
    <measure>propofol consumption</measure>
    <time_frame>60 minutes</time_frame>
    <description>Number of patients in each group who had to receive propofol due to loss of cooperation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Endoscopist Satisfaction</measure>
    <time_frame>60 min</time_frame>
    <description>Endoscopist Satisfaction scored from 1-10</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Patient's Recall.</measure>
    <time_frame>6 hours</time_frame>
    <description>Any recall and unpleasantness related to recall will be noted</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>6 hours</time_frame>
    <description>Patient satisfaction. Will be tested on a numerical scale from 0 (not satisfied at all) to 10 (fully satisfied) at the time of discharge from the hospital.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side effects</measure>
    <time_frame>6 hours</time_frame>
    <description>Side Effects noted in each group for example excessive sedation, nausea, vomiting, pruritis, respiratory depression or apnoea.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Colonoscopy</condition>
  <arm_group>
    <arm_group_label>Midazolam and Fentanyl</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Midazolam and Fentanyl Two minutes before the colonoscopy procedure, a bolus of midazolam 0.03mg/Kg and 1.5microgram/Kg fentanyl will be given intravenously over 60 sec in group 1. 0.5 mg of midazolam intravenously can be given every two minutes till the patient is sufficiently sedated (sleeping but arousable on calling). The colonoscopy can start at this end point. Increments of 0.5mcg/Kg of fentanyl will be given if patient complains of pain, which can be repeated every 5 minutes if there is persistent pain</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Midazolam and Remifentanil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Midazolam and Remifentanil Target controlled infusion of Remifentanil to 3.0 ng/ml will be started 2 minutes before procedure. The patient will then be given same doses of midazolam in 0.5 mg increments till sedated sufficiently (sleeping but arousable on verbal command). During Colonoscopy the dose of Remifentanil could be increased by 0.5ng/ml if patient complained of pain upto 4.0ng/ml.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Remifentanil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Remifentanil Group Patients will receive only Remifentanil in the same doses as given in group 2. During the procedure if the pain is excessive and persistent in spite of increasing the respective doses as prescribed in each group, or causing loss of cooperation of patient and interfering in the performance of procedure, the patients will be given sleep dose of Inj Propofol and further anaesthesia care as required will be provided for same.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam, Fentanyl</intervention_name>
    <description>Two minutes before the colonoscopy procedure, a bolus of midazolam 0.03mg/Kg and 1.5microgram/Kg fentanyl will be given intravenously over 60 sec in group 1. 0.5 mg of midazolam intravenously can be given every two minutes till the patient is sufficiently sedated (sleeping but arousable on calling). The colonoscopy can start at this end point. Increments of 0.5mcg/Kg of fentanyl will be given if patient complains of pain, which can be repeated every 5 minutes if there is persistent pain.</description>
    <arm_group_label>Midazolam and Fentanyl</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam, Remifentanil</intervention_name>
    <description>The patient in group 2 Target controlled infusion of Remifentanil to 3.0 ng/ml will be started 2 minutes before procedure. The patient will then be given same doses of midazolam in 0.5 mg increments till sedated sufficiently (sleeping but arousable on verbal command). During Colonoscopy the dose of Remifentanil could be increased by 0.5ng/ml if patient complained of pain upto 4.0ng/ml.</description>
    <arm_group_label>Midazolam and Remifentanil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Remifentanil</intervention_name>
    <description>The group 3 patient will receive only Remifentanil in the same doses as given in group</description>
    <arm_group_label>Remifentanil</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients between 18-75 years&#xD;
&#xD;
          2. ASA Grade I, II and controlled ASA III.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient Refusal&#xD;
&#xD;
          2. Patients with psychiatric or Emotional Disorders&#xD;
&#xD;
          3. Previous adverse reaction to any of the drugs used&#xD;
&#xD;
          4. History of addiction to opiates/sedatives/alcohol&#xD;
&#xD;
          5. ASA Grade 3-4 patients with clinically significant or uncontrolled cardiovascular or&#xD;
             respiratory disease.&#xD;
&#xD;
          6. Pregnancy&#xD;
&#xD;
          7. Age &lt;=18years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Reeta Singh, MD DNBE MBA</last_name>
    <role>Principal Investigator</role>
    <affiliation>Awali Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Awali Hospital</name>
      <address>
        <city>Manama</city>
        <zip>945</zip>
        <country>Bahrain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bahrain</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 24, 2015</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>October 22, 2019</last_update_submitted>
  <last_update_submitted_qc>October 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Remifentanil</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03037892
org study id: KHUH/Research/No.89/2015
nct id: NCT03037892
lead sponsor: 
has dmc: Yes
Colonoscopy is one of the most commonly performed outpatient procedure for diagnosis and
      treatment of lower gastrointestinal tract disorders. It has been largely accepted as an
      effective tool for colorectal cancer(CRC) screening, given its ability to detect and remove
      identified polyps. Increased colonoscopy utilization is associated with the observed decline
      in the incidence of CRC and its diagnosis at earlier stages. Diagnostic and therapeutic
      colonoscopy can successfully be performed using moderate sedation in the ambulatory setting.
      Techniques of sedation must guarantee the comfort and safety of patients, and at the same
      time allow a rapid turnover of patients.. An anaesthetic agent with rapid onset and offset of
      action, and convenient titration of anaesthetic/analgesic depth as well as rapid recovery to
      enable discharge from the endoscopy unit as soon as possible would be ideal as most such
      procedures are performed in the Non-Operating Room Anaesthesia(NORA) settings.

      There is recent interest in the use of Remifentanil, in endoscopic units as it might have
      advantages over other drugs because of its profound analgesic effects, rapid onset and offset
      time and rapid titration to the individual patient's requirements and intermittent pain
      during colonoscopy.

      The aim of this randomized study is to test the hypothesis that a colonoscopy of good quality
      in terms of pain relief, patient comfort and discharge times with less cardiorespiratory side
      effects can be performed using Remifentanil as a sole agent as compared with the standard
      midazolam/fentanyl protocol. The second group combining Remifentanil with Midazolam is taken
      to evaluate if there is any advantage of adding an anxiolytic amnesic drug as used in the
      standard Midazolam/Fentanyl Protocol.
A Prospective Randomized Comparative Study to Evaluate the Use of Remifentanil as a Sole
      Agent or in Combination with Midazolam Versus Fentanyl/Midazolam during Sedation for
      Colonoscopy.

      Background:

      Audits of patient experiences and studies on quality improvement for colonoscopy have shown
      that increased sedation administration results in long-lasting improvement of colonoscopy
      quality indicators. However deep sedation in NORA ambulatory settings has been associated
      with increased sedation associated risks and raises costs for healthcare providers. Sedation
      may delay discharge of patients or cause discharge of patients with early cognitive
      impairment that contraindicate complex activities of daily living, The search is still on for
      an ideal drug that produces optimal operating conditions with minimum postoperative cognitive
      impairment.

      Remifentanil is an ultrashort, very potent narcotic, which is eliminated by plasma and tissue
      esterases. There is recent interest in the use of Remifentanil in endoscopic units as it
      might have advantages over other drugs because of its profound analgesic effects, rapid onset
      and offset time and rapid titration to the individual patient's requirements and intermittent
      pain during colonoscopy. There are a few studies which suggest that the
      analgosedation(intense pain relief without loss of consciousness) achievable with
      remifentanil is a valid alternative to the present sedo-analgesia techniques used for
      colonoscopic sedation.

      Ackcaboy ZN conducted a prospective randomized trial to test the hypothesis that continuous
      infusion of low dose remifentanil (0.05mcg/kg/min) continuous and bolus injection - in
      combination with 2 mg of midazolam, can provide effective analgesia, sedation, amnesia,
      patient comfort and stable recovery profile without respiratory depression when compared with
      Propofol infusion during colonoscopy.

      Following Moerman's hypothesis: "If pain is the crucial point, why do we need sedation?", the
      use of remifentanil as a sole agent for colonoscopy, has been investigated and compared with
      the sedative scheme of midazolam plus pethidine. Remifentanil was found to provide sufficient
      pain relief with better hemodynamic stability, less respiratory depression, and significantly
      faster recovery and hospital discharge than moderate sedation with midazolam and pethidine.
      Midazolam-Fentanyl and Midazolam-Remifentanyl techniques has been compared for Endoscopic
      Retrograde Cholangio- Pancreatography another painful endoscopic procedure and there were
      definite advantages seen in the midazolam-remifentanil group in level of sedation and patient
      satisfaction. However, remifentanil use is not widespread and is being used only by
      anaesthesiologists.

      There is scope to conduct further studies to ascertain if there is an actual real benefit of
      using remifentanil as a sole agent or in combination with midazolam, over the standard
      technique of midazolam/fentanyl used in endoscopy units.

      This Controlled Randomized Clinical Study is planned to evaluate whether Remifentanil by
      itself as a sole agent or in combination with Midazolam provides a safe and effective
      sedation for colonoscopy as compared to the present technique of midazolam and fentanyl being
      used by most endoscopists.

      1. Statement of the problem Colonoscopy is a proven method for bowel cancer screening and is
      often experienced as a painful procedure. They are the most frequently performed endoscopic
      procedures. However motivating patients to participate in colonoscopy screening continues to
      be a challenge as it is associated with considerable anxiety and pain. Additionally patients
      complain of disruption of normal activities by bowel preparations and hangover effects from
      sedation and need for an escort after procedure. The sedation protocol are followed by the
      endoscopists' themselves with a nurse who is monitoring the case. Rescue from extreme
      sedation or agitation is not uncommon. Ideal sedation should be potent and easily titrated ,
      be adequate and safe for the painful procedure yet have a quick recovery for an early
      discharge as these procedures are usually done in an ambulatory setting.

      Remifentanyl is a relatively new drug which has been used in endoscopic suites with some
      advantage. There is scope to conduct further studies to ascertain if there is an actual real
      benefit of using remifentanil as a sole agent or in combination with midazolam, over the
      standard technique of midazolam/fentanyl..

      Significance of the problem

      Colonoscopy is one of the most commonly performed outpatient procedure for diagnosis and
      treatment of lower gastrointestinal tract disorders, usually performed under moderate
      sedation in the ambulatory setting. As pain and vasovagal reactions are common during the
      procedure, administration of sedation and analgesia is imperative. Techniques of sedation
      must guarantee the comfort and safety of patients, and at the same time allow a rapid
      turnover of patients. An anaesthetic agent with rapid onset and offset of action, and
      convenient titration of anaesthetic/analgesic depth as well as rapid recovery to enable
      discharge from the endoscopy unit as soon as possible would be ideal.

      There is recent interest in the use of Remifentanil in endoscopic units as it might have
      advantages over other drugs because of its profound analgesic effects, rapid onset and offset
      time and rapid titration to the individual patient's requirements and intermittent pain
      during colonoscopy. Remifentanil was found to provide sufficient pain relief with better
      hemodynamic stability, less respiratory depression, and significantly faster recovery and
      hospital discharge than moderate sedation in a few preliminary studies.

      Objectives of the study:

      General objective:

      The study plans to study whether Remifentanil by itself as a sole agent or in combination
      with Midazolam provides a safe and effective sedation for colonoscopy as compared to the
      present technique of midazolam and fentanyl being used by the endoscopists.

      Specific objective:

        -  Whether remifentanyl as a sole agent was effective and safe for Colonoscopies, or if
           combined with midazolam offered any advantages over the only remifentanyl or standard
           midazolam fentanyl technique.

        -  Effectiveness will be judged by the number of patients who complained of pain during
           procedure, number of patients who became uncooperative during the technique and had to
           be given Propofol to convert it into a general anaesthetic.

        -  Safety will be judged by any significant haemodynamic or respiratory changes and changes
           in sedation level in the various study groups.

        -  Advantages in reduced recovery time will be noted from the time to full recovery after
           sedation procedure.

        -  Patient and Endoscopist's satisfaction score will be recorded to see any differences in
           the three groups.

      Method:

      Following an Ethics Committee approval, 90 patients who are undergoing colonoscopy under
      moderate sedation in an ambulatory setting at Awali Hospital will be included in the study
      who satisfy the inclusion/exclusion criteria. Informed Consent will be taken preoperatively
      and they will be randomly allocated in to three groups as follows:

      Group 1 - Patients will receive Midazolam and Fentanyl.

      Group 2 - Patients will receive Midazolam and Remifentanil

      Group 3 - Patients will receive Remifentanil as a sole agent

      Study subjects: Inclusion and exclusion criteria of the study subjects.

      Design: Prospective, randomized controlled clinical trial

      Sample size: 90 patients will be selected for the study randomly dividing them into the three
      groups of 30 each.

      Sampling technique: All patients due for colonoscopy under moderate sedation who satisfy the
      inclusion and exclusion criteria and who agree to be part of the study group by an informed
      consent will be randomly divided into the three groups of 30 each.

      Randomization will be done by making identical folded slips of the three groups and by
      randomly picking up a slip preoperatively on the morning of procedure for each patient.

      Timeframe of the study. The study will be done prospectively once approved by the Ethics
      Committee and registered as a Prospective Clinical Trial in the Registry

      Data Collection methods, instruments used and measurements: Describe the instruments to be
      used for data collection (questionnaire, observation recording form, etc.)

      Study Protocol:

      Patients undergoing elective colonoscopy who satisfy the inclusion criteria will be randomly
      allocated to the 3 groups after taking an informed consent. All colonoscopies will be
      performed by two Endoscopists of Awali Hospital who seem to work in a very similar manner for
      colonic endoscopy.

      On arrival to the endoscopy room an IV access will be established. Supplemental oxygen 3
      L/min will be given through both the nostrils and mouth by a specially designed mask which
      can monitor the end tidal CO2 level. The basal values of noninvasive blood pressure (NIBP),
      peripheral oxygen saturation (SpO2), heart rate (HR), respiratory rate (RR) and end-tidal CO2
      level (ETCO2) will be noted.

      Two minutes before the colonoscopy procedure, a bolus of midazolam 0.03mg/Kg and
      1.5microgram/Kg fentanyl will be given intravenously over 60 sec in group 1. 0.5 mg of
      midazolam intravenously can be given every two minutes till the patient is sufficiently
      sedated (sleeping but arousable on calling). The colonoscopy can start at this end point.
      Increments of 0.5mcg/Kg of fentanyl will be given if patient complains of pain, which can be
      repeated every 5 minutes if there is persistent pain. The patient in group 2 Target
      controlled infusion of Remifentanil to 3.0 ng/ml will be started 2 minutes before procedure.
      The patient will then be given same doses of midazolam in 0.5 mg increments till sedated
      sufficiently (sleeping but arousable on verbal command). During Colonoscopy the dose of
      Remifentanil could be increased by 0.5ng/ml if patient complained of pain upto 4.0ng/ml. The
      group 3 patient will receive only Remifentanil in the same doses as given in group 2. During
      the procedure if the pain is excessive and persistent in spite of increasing the respective
      doses as prescribed in each group, or causing loss of cooperation of patient and interfering
      in the performance of procedure, the patients will be given sleep dose of Inj Propofol and
      further anaesthesia care as required will be provided for same.

      The Haemodynamic Parameters(NIBP,HR), RR, SPO2, Sedation Scare (Ramsay) and ETCO2 will be
      measured 1 and 3 min after the drug dose then every 5 min till end of procedure. After
      procedure the patients will be shifted to recovery and the same parameters will continue to
      be measured every 5 min until discharge from the 30 min stay in the recovery room. Pain
      Scoring will be done by a Visual Analog Pain Score (VAS) (0- minimum to 100mm- Maximum pain)
      just after passing the scope, during the scope, just after the completion of colonoscopy and
      at the discharge from the recovery unit.

      Total amount of drug consumed, duration of colonoscopy, incidence of adverse effects
      (desaturation <94% on Pulseoximetry, Hypoventilation (RR<8/min or apneic episode, hypotension
      (SBP<90mm Hg), nausea vomiting or pruritis will be recorded.

      Patient satisfaction will be noted at the time of discharge from ward

      Primary Outcome Measures:

      • The Recovery Time The patient will be considered recovered if and when they achieve an
      Aldrete score of 10. Aldrete scoring will be done every 5 minutes after completing
      colonoscopy up to 30 min or till achievement of a 10/10 Aldrete Score.

      Aldrete score

        -  Respiration: Able to take deep breath and cough = 2, Dyspnea/shallow breathing = 1,
           Apnea = 0

        -  O2 saturation: Maintains > 92% on room air =2, Needs O2 inhalation to maintain O2
           saturation > 90% =1 , O2 saturation < 90% even with supplemental oxygen =0

        -  Consciousness: Fully awake= 2, Arousable on calling = 1, Not responding = 0

        -  Circulation: BP +/- 20 mm Hg preop =2, BP +/- 20-50 mm Hg preop =1, BP +/- 50 mm Hg
           preop =0

        -  Activity: Able to move 4 extremities = 2, Able to move 2 extremities = 1, Able to move 0
           extremities 0

        -  Participants Assumed to Feel Frequent Pain, during and after colonoscopy. • Patients
           sound "Ah" at feeling pain during colonoscopy would be taken as a measure: if a patients
           sounds "Ah" > 6 times, the patient was assumed to feel frequent pain. Will be scored as
           0 no pain ,1if he complains of pain or 2 if he says Ah or complains of pain frequently,
           that is, more than 6 times.

        -  Patient's Distress Score every 5 min till the end of colonoscopy. Patients' distress as
           minimal, mild moderate or severe distress.

        -  Number of patients in each group who had to receive propofol due to loss of cooperation

      Secondary Outcome Measures:

        -  Endoscopist Satisfaction. Time Frame: 5 min after the colonoscopy. Endoscopist's
           satisfaction after colonoscopy in visual analogue scale 100 mm

        -  Incidence of Patient's Recall. Tested after colonoscopy before discharge from the
           hospital. The numbers of patients who recalled instructions and explanations given
           during colonoscopy will be noted and if there was any unpleasantness related to the
           recall or awareness.

        -  Patient satisfaction. Will be tested on a numerical scale from 0 (not satisfied at all)
           to 10 (fully satisfied) at the time of discharge from the hospital.

        -  Side Effects noted in each group for example excessive sedation, nausea, vomiting,
           pruritis, respiratory depression or apnoea.

      The data will be statistically analyzed, to arrive at a conclusion on whether remifentanyl as
      a sole agent was effective for Colonoscopies, or if combined with midazolam offered any
      advantages over the only remifentanyl or standard midazolam fentanyl technique.

      Implications of the study results to population health and health system policy in Awali
      Hospital and Bahrain:
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: The Recovery Time
time frame: 30 min
description: Every 5 minutes till a score of 10/10 achieved on Aldrete Score
measure: propofol consumption
time frame: 60 minutes
description: Number of patients in each group who had to receive propofol due to loss of cooperation
measure: Endoscopist Satisfaction
time frame: 60 min
description: Endoscopist Satisfaction scored from 1-10
measure: Incidence of Patient's Recall.
time frame: 6 hours
description: Any recall and unpleasantness related to recall will be noted
measure: Patient satisfaction
time frame: 6 hours
description: Patient satisfaction. Will be tested on a numerical scale from 0 (not satisfied at all) to 10 (fully satisfied) at the time of discharge from the hospital.
measure: Side effects
time frame: 6 hours
description: Side Effects noted in each group for example excessive sedation, nausea, vomiting, pruritis, respiratory depression or apnoea.
arm group label: Midazolam and Fentanyl
arm group type: Active Comparator
description: Midazolam and Fentanyl Two minutes before the colonoscopy procedure, a bolus of midazolam 0.03mg/Kg and 1.5microgram/Kg fentanyl will be given intravenously over 60 sec in group 1. 0.5 mg of midazolam intravenously can be given every two minutes till the patient is sufficiently sedated (sleeping but arousable on calling). The colonoscopy can start at this end point. Increments of 0.5mcg/Kg of fentanyl will be given if patient complains of pain, which can be repeated every 5 minutes if there is persistent pain
arm group label: Midazolam and Remifentanil
arm group type: Experimental
description: Midazolam and Remifentanil Target controlled infusion of Remifentanil to 3.0 ng/ml will be started 2 minutes before procedure. The patient will then be given same doses of midazolam in 0.5 mg increments till sedated sufficiently (sleeping but arousable on verbal command). During Colonoscopy the dose of Remifentanil could be increased by 0.5ng/ml if patient complained of pain upto 4.0ng/ml.
arm group label: Remifentanil
arm group type: Experimental
description: Remifentanil Group Patients will receive only Remifentanil in the same doses as given in group 2. During the procedure if the pain is excessive and persistent in spite of increasing the respective doses as prescribed in each group, or causing loss of cooperation of patient and interfering in the performance of procedure, the patients will be given sleep dose of Inj Propofol and further anaesthesia care as required will be provided for same.
intervention type: Drug
intervention name: Midazolam, Fentanyl
description: Two minutes before the colonoscopy procedure, a bolus of midazolam 0.03mg/Kg and 1.5microgram/Kg fentanyl will be given intravenously over 60 sec in group 1. 0.5 mg of midazolam intravenously can be given every two minutes till the patient is sufficiently sedated (sleeping but arousable on calling). The colonoscopy can start at this end point. Increments of 0.5mcg/Kg of fentanyl will be given if patient complains of pain, which can be repeated every 5 minutes if there is persistent pain.
arm group label: Midazolam and Fentanyl
intervention type: Drug
intervention name: Midazolam, Remifentanil
description: The patient in group 2 Target controlled infusion of Remifentanil to 3.0 ng/ml will be started 2 minutes before procedure. The patient will then be given same doses of midazolam in 0.5 mg increments till sedated sufficiently (sleeping but arousable on verbal command). During Colonoscopy the dose of Remifentanil could be increased by 0.5ng/ml if patient complained of pain upto 4.0ng/ml.
arm group label: Midazolam and Remifentanil
intervention type: Drug
intervention name: Remifentanil
description: The group 3 patient will receive only Remifentanil in the same doses as given in group
arm group label: Remifentanil
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Reeta Singh, MD DNBE MBA
role: Principal Investigator
affiliation: Awali Hospital
facility: 
country: Bahrain
responsible party type: Sponsor
mesh term: Fentanyl
mesh term: Midazolam
mesh term: Remifentanil