Atomized Intranasal Vs Intravenous Ketorolac in Acute Renal Colic Pain Management.
Condition: Acute Renal Colic
MeSH terms: Colic; Renal Colic
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Introduction: Pain is a common reason for individuals to seek health care, especially
      emergency care. Ketorolac has numerous advantages over other pain medications, especially the
      opioids. The intranasal administration of ketorolac has been shown to be safe and effective
      in the treatment of postoperative pain following major abdominal surgery and post dental
      surgery, but there have been no studies evaluating the use of intranasal ketorolac for the
      treatment of acute renal colic pain in the emergency department.

      Methods: This is a double blinded randomized controlled trial. two hundred renal colic
      patients presented to the emergency department will be randomized to intervention (30 mg
      intranasal ketorolac) and (30mg intravenous ketorolac) case groups. Their pain before and
      after receiving ketorolac will be measured by visual Analog Scale (VAS pain score). Patient,
      attending physician and administering nurse will be blinded throughout the study. The
      analgesic effects will be assessed by several measures including pain relief, pain intensity
      difference, global pain evaluation, global assessment of analgesia, and the summed pain
      intensity difference. The safety will be assessed by documentation of adverse events, vital
      signs, and clinical assessment before and after drug administration.

      Aim: The aim of this study is to compare analgesic effects of intranasal Ketorolac
      tromethamine versus intravenous Ketorolac tromethamine in adult patients with moderate to
      severe renal colic.

      Primary Objective: Analgesic effects of Intranasal Ketorolac on the visual analog scale
      (VAS).

      Secondary Objectives: Adverse Events, the need of rescue pain medications, time to discharge
      and recurrent visit within 24 hours.

      Patient Population: Adults (from age 18 to 64 years) who presents to emergency department
      (ED) at Sultan Qaboos University Hospital with moderate to severe acute flank pain suggestive
      of renal colic (visual analog scale 7 or more).

      Intervention: Single dose of intranasal ketorolac 30mg.

      Clinical measurement: Visual Analog Scale will be assessed at 0, 30 and 60 minutes after
      intervention. Number and dosage of rescue medication, any reported events by patient or
      attending physician will be documented.

      Outcome: Decrease in pain measures by VAS pain score after intranasal ketorolac is given,
      tolerability and safety evaluation.
    

Detailed description: 
      Research objectives and hypothesis:

      The aim of this study is to compare the analgesic effects of intranasal Ketorolac
      tromethamine versus intravenous Ketorolac tromethamine in adult patients with moderate to
      severe renal colic seen at the Emergency Department at Sultan Qaboos University Hospital.

      Study design:

      Prospective double-blinded randomized clinical trial in adults (from age 18 to 64 years) who
      presents to the emergency department (ED) at Sultan Qaboos University Hospital with moderate
      to severe acute flank pain suggestive of renal colic (visual analog scale 7 or more). Written
      consent will be obtained from the patient. Eligible subjects will be enrolled (see section
      5).

      Control Group Will receive 30 mg intravenous ketorolac in 10 ml syringe + 1 ml Normal Saline
      9% using the intranasal device (0.5 ml in each nostril).

      Intervention Group Will receive 30 mg intranasal ketorolac in 1 ml intranasal device (0.5 ml
      in each nostril) + 10 ml Intravenous Normal Saline 9%.

      Primary endpoint:

      Analgesic effects of Intranasal Ketorolac on the visual analog scale (VAS). Change in visual
      analog scale after receiving intranasal ketorolac. 0 (no pain) - 10 (worst possible pain).

      Secondary endpoint:

        -  Adverse Event/Side Effects.

        -  Safety assessed by reporting all adverse events.

        -  The need of rescue pain medications.

        -  Time to discharge.

        -  Recurrent visit within 24 hours.

      Sample size:

      after 1 hour follow-up, 146 patient will be needed ( 73 on each arm) to have 90% power to
      detect a difference of a 0.7 of the response of visual analog scale score ( which usually
      ranges between 0 and 10 ) between the groups (5.3 vs 4.6) at the 5% alpha (significance)
      level. Because of missing data and losses to follow-up, an additional 54 subjects will be
      needed (100 in each arm) for a total of 200 subjects (study sample). A P-value <0.5. Level of
      significance to be used.

      Study Procedures:

        1. Present to the Clinical Site Adult subjects ages 18 to 64 years with a classical
           presentation of acute renal colic being seen in the emergency department may be eligible
           for this study.

           Clinical sign and symptoms

             -  Severe flank pain radiating inferiorly and anteriorly with or without:

             -  Nausea and vomiting.

             -  Urinary symptoms.

             -  Previous history of renal colic.

        2. Eligibility Assessments Inclusion and exclusion criteria will be check.

        3. Informed Consent Potentially eligible participants will be identified by their treating
           clinicians. Written informed consent to participate in this study will follow a process
           of information exchange between clinicians and potential participants.

        4. Study Pain Assessments

           Three pain assessments will be done based on VAS-Pain at:

             -  0 minutes

             -  30 minutes

             -  60 minutes Pain scores will be recorded and documented before the administration of
                medication for a baseline pain assessment and at specified intervals after the
                administration. Post-treatment pain scores will be recorded at 0, 30 and 60
                minutes. Pain assessments will be by the Visual Analog Scale for Pain. It is
                usually presented as a 10cm horizontal line on which the patient's pain intensity
                is represented by a point between the extremes of "no pain at all" and "worst pain
                imaginable." All patients must have a minimum of two pain scores. If rescue
                medications were given, a VAS-Pain will be obtained immediately prior to treatment.

        5. Standard-of-Care Procedures: Pain Management Patients may receive additional medications
           as part of their emergency department treatment including additional pain medications,
           such as opioids. Any additional medications administered will be recorded. The need for
           additional medications (including the drug administered, the dose, the time, and the
           route of administration) will be recorded.

        6. Safety Assessments All adverse events will be documented on an adverse event case log.
           Serious adverse events should be immediately reported to the primary investigator. Any
           serious, adverse event will be reported immediately to the Institutional Review Board.

      Adverse Events is considered serious if it causes a threat to the patient's life or
      functioning. The U.S. Food and Drug Administration (FDA) defines a serious adverse event
      (SAE) as any untoward medical occurrence that:

        -  Results in death.

        -  Life-threatening (places the patient at risk of death).

        -  Requires hospitalization or prolongs an existing hospitalization.

        -  Causes persistent or significant disability or incapacity.

        -  Requires medical intervention to prevent one of the above outcomes.

      RISKS AND BENEFITS Ketorolac has been proven effective for pain relief, especially for
      certain types of pain, such as musculoskeletal pain, headaches and the pain from renal colic.
      Inappropriate patients, ketorolac is a relatively safe drug for the treatment of pain. Side
      effects and complications, such as gastrointestinal complaints (e.g. abdominal pain,
      dyspepsia, GI bleeding) and renal dysfunction (elevation of the blood urea nitrogen and
      creatinine) have been reported but with appropriate patient's selection are uncommon or rare.
      The use of NSAIDS including ketorolac is not recommended in patients with active peptic ulcer
      disease, renal disease or at risk for renal failure due to volume depletion, cerebrovascular
      bleeding, hemorrhagic disorders, or those with a high risk of bleeding. With an appropriate
      patient selection, ketorolac can be a safe and effective medication for the relief of pain.
      The drug used in this study has a very low risk of developing any complications. However,
      during visits patients will be monitored for any complications and all adverse effects if any
      will be reported. With the proposed hypothesis, intranasal has the potential to reduce opioid
      use in the ED, provides fast, needleless and easy methods to apply. It will decrease the
      waiting time, cannulation and unnecessary blood investigations in patients with a classic
      presentation of acute renal colic.
    

Intervention name(s): Intravenous Ketorolac Tromethamine; Intranasal Ketorolac Tromethamine
Intervention type(s): Drug; Drug
Intervention description(s): 30 mg ketorolac single dose; 30 mg ketorolac single dose
Other intervention name(s): ketorolac injection; Atomized Intranasal Ketorolac
Intervention MeSH terms: Ketorolac; Ketorolac Tromethamine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: case-control trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment