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"THINK Trial: Treatment of Headache With IntraNasal Ketamine: A Randomized Controlled Trial Evaluating the Efficacy of Intranasal Ketamine Versus Standard Therapy in the Management of Primary Headache Syndromes in the Emergency Department" (THINK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03081416
Recruitment Status : Completed
First Posted : March 16, 2017
Last Update Posted : January 18, 2018
Sponsor:
Information provided by (Responsible Party):
Danny Villalobos, Brooke Army Medical Center

Tracking Information
First Submitted Date  ICMJE March 10, 2017
First Posted Date  ICMJE March 16, 2017
Last Update Posted Date January 18, 2018
Actual Study Start Date  ICMJE May 2016
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2017)
VAS 30 min [ Time Frame: 30 min ]
Change in Visual Analogue Score at 30 minutes
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2017)
  • VAS 60 min [ Time Frame: 60 min ]
    Change in Visual Analogue Score at 60 minutes
  • NRS at discharge [ Time Frame: Discharge ]
    Numerical Rating Scale at discharge
  • NRS 24 hours [ Time Frame: 24 hours ]
    Pain NRS score at 24 hours post discharge
  • NRS 72 Hours [ Time Frame: 72 Hours ]
    Pain NRS score at 72 hours post discharge
  • Side effects [ Time Frame: At 15 min then at 30 min intervals while in the ED ]
    Side effects reported by patients in both treatments arms
  • Repeat ED/primary care encounters [ Time Frame: 24 and 72 hours ]
    Need for repeat patient evaluation at 24-72 hours
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE "THINK Trial: Treatment of Headache With IntraNasal Ketamine: A Randomized Controlled Trial Evaluating the Efficacy of Intranasal Ketamine Versus Standard Therapy in the Management of Primary Headache Syndromes in the Emergency Department"
Official Title  ICMJE "THINK Trial: Treatment of Headache With IntraNasal Ketamine: A Randomized Controlled Trial Evaluating the Efficacy of Intranasal Ketamine Versus Standard Therapy in the Management of Primary Headache Syndromes in the Emergency Department"
Brief Summary This is a randomized, single-blind, placebo controlled trial to evaluate the efficacy of sub-dissociative dose ketamine versus standard care therapy for acute headache management of in patients presenting to the emergency department with headache as the chief compliant.
Detailed Description

This is a randomized, single-blind, placebo controlled trial to evaluate the efficacy of sub-dissociative dose ketamine versus standard care therapy for acute headache management of in patients presenting to the emergency department with headache as the chief compliant. Standard care will include 25 mg of diphenhydramine (DIP) IV, 10 mg of metoclopramide (MET) IV, +/- 15-30 mg ketorolac and +/- 10 mg of dexamethasone (DEX) IV the discretion of the treating provider. This study has been approved by Brooke Army Medical Center (BAMC) institutional review board and clinicaltrials.gov registration is pending.

A convenience sample of patients 18 to 65 years of age with a chief complaint of headache will be considered for enrollment. Potential subjects are those presenting to the SAMMC ED with a chief complaint of headache. Attempts to engage subjects earlier in their ED Course (EDC) will be made. This will mitigate interruptions in the subject's EDC, possible withdrawals from the control group, and lack of subject interest in the study. The triage nurse will inform the PI or AI of any patient presenting to the ED with a chief complaint of headache. Patients meeting inclusion criteria will be provided with a brochure briefing them on the study. If they are willing to participate, then a member of the research team will obtain written consent.

Patient screening, enrollment, patient consents, and data collection will be performed by the PI or AI. Each AI will complete training regarding study details, inclusion/exclusion criteria, atomization, intranasal delivery, and ketamine pharmacokinetics which will be conducted by the PI.

Once a patient is consented the team member will obtain a study packet, and the patient will be assigned a study identification number. The study packet will contain the required forms, surveys, Wand documentation forms. The study personnel will then write on the patient's standard order sheet "SDDK Protocol, Patent #__, __kg"

All females of child-bearing age that have not had a hysterectomy or tubal ligation will receive a pregnancy test. This is a standard test performed in the ED and considered part of routine practice. A pregnancy test in females is one test that is required by all patients undergoing this clearance among other labs not applicable to this study.

Baseline pain score will be determined using a 100 mm visual analogue scale, described to the patient as "no pain" being 0 and "the worst pain imaginable" being 100. A patient will be determined as eligible for enrollment if a baseline VAS score of 50 or greater is reported. A study investigator will then record the patient's body weight and baseline vital signs. Additional demographics recorded will include age, gender, comorbid medical conditions and headache classification.

Once the subject is determined to meet the inclusion/exclusive criteria and has agreed to participate in the study and has a signed consent form, the patient will be randomized via permutated-block randomization into the ketamine or standard care treatment group. An intravenous catheter will be initiated in each subject and 1000 mL normal saline IV bag will started on each patient per provider discretion.62 Once the medication of either treatment arm has been obtained and is ready to administer the PI or AI will document time zero.

The standard care arm will be administered 10mg of MET, 25 mg of DIP and +/- 15-30 mg of KET and +/- 10mg of dexamethasone IV push. 10 mg of MET will be added to the 1000 mL normal saline bag and infused as a bolus until the 1000 mL normal saline bag is empty. In addition, the standard care arm will be administered same volume of atomized intranasal normal saline as calculated dose of 0.75mg/kg ketamine.

The Ketamine arm will be administered intranasal SDDK via atomizer based on previous studies regarding intranasal ketamine administration in the ED at an initial dose of 0.75 mg/kg.2 The treating nurse will prepare the SDDK using the weight based dosing table found in each study packet. The treating nurse will give the syringe with the SDDK to the AI/PI for verification and administration. Each patient will also be administered 0.5ml, 0.5-1ml and 2.5ml normal saline boluses in place of the DIP, +/- KET and +/- DEX for a maximum of three boluses. An additional 2ml normal saline bolus will be added to the 1000 mL normal saline bag in place of the MET and the 1000 mL normal saline bag will be infused as a bolus until the bag is empty. Approximately 30 minutes after initial ketamine administration, study subjects will be asked if they would like an additional dose of medication for their headache. If the study subject request additional medication, the patient can receive a single repeat dose of 0.25mg/kg intranasal ketamine . This time was chosen empirically as reasonable time frame for clinic reassessment of analgesic affect.

60 minutes after all medications are given, subject participation in the study will be concluded and routine ED care will be resumed. At this time each subject will be asked if they would like additional medication for the treatment of their headache. If they would like additional medication, rescue analgesia may be given at the discretion of the ED provider managing the patient. Also, at any point the treating provider feels analgesia is inadequate either by patient verbalization or provider assessment, rescue medications may be provided at the treating provider's discretion.

Study investigators will record treatment arm pain scores, vital signs, and adverse effects at 10, 30, 60 and 90 minutes. Total hospital course time will also be documented. Adverse effects recorded will be based on the Side Effects Rating Scale for Dissociative Anesthetics (SERDA) and will include fatigue, dizziness, nausea, headache, feelings of unreality, changes in hearing, mood change, general discomfort and hallucinations. Although SERDA is frequently reported on a five point scale, patients will be graded on the adverse effects by answering "yes" or "no". An adverse effect will be considered serious if they resulted in clinical symptoms that were unable to be abated with clinical intervention or the tincture of time.

At the time of discharge, a final pain score will be recorded using the 10 point numerical rating score (NRS) with 0 meaning 'no pain' and 10 meaning "the worse pain possible." Patients will also be asked if they believed they got the study drug or standard care. A final ED encounter satisfaction score will be recorded using a the 10 point numerical rating score (NRS) with 0 meaning ' Very dissatisfied' and 1-0 meaning "Very satisfied." Follow-up will occur via telephone using the scripted phone conversation (included in this package) at 48-72 hours post-discharge. All subjects will be queried via a scripted interview for any adverse effects using the SERDA elements and whether the patient continues to perceive headache pain and duration of previous headache relief. Again, pain will be assessed using the 10 point NRS. Additional information will be collected via follow up communication including, but not limited to changes in medications, new diagnoses, unplanned visits or admissions.

Subject will be asked for contact information including phone numbers and email addresses for follow-up. Phone contact will be the primary method of contact. If, after two phone call attempts, the PI is unsuccessful at establishing patient contact, a scripted email be sent requesting the subject contact the protocol staff to complete the survey. If patients are unable to be contacted or lost to follow-up medical records will be queried for additional contact phone numbers if available. Veteran's Affairs system will be searched if all other methods are exhausted without result. The protocol team will attempt to contact the patient for 5 days after their hospital discharge date. If the patient has not been contacted by this time frame subjects will assumed to be lost to follow-up.

The primary outcome will be the change in pain level as documented by the VAS from study initiation to discharge. Secondary outcomes will include treatment efficiency (time to pain relief), change of pain score from discharge to follow up and side effects profile using the SERDSA questionnaire. All research will be completed when either the PI or AI are available in the ED to enroll and consent patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Two arm-Randomized placebo controlled
Masking: Single (Participant)
Masking Description:
Placebo controlled
Primary Purpose: Treatment
Condition  ICMJE
  • Headache
  • Intranasal Ketamine
Intervention  ICMJE
  • Drug: Ketamine
    Intranasal ketamine administration
  • Drug: Normal saline
    Other Name: Placebo
  • Drug: Metoclopramide
    Standard therapy
    Other Name: Standard therapy
  • Drug: Ketorolac
    standard therapy
  • Drug: Dexamethasone
    Standard therapy
  • Drug: Benadryl
    Standard therapy
Study Arms  ICMJE
  • Experimental: Intranasal Ketamine arm
    Intranasal ketamine administered to participant
    Interventions:
    • Drug: Ketamine
    • Drug: Normal saline
  • Active Comparator: Standard Therapy
    Reglan 10 mg; Benadryl 25 mg administered to all participants Toradol 15-30 mg; dexamethasone 10 mg added at treating providers discretion.
    Interventions:
    • Drug: Metoclopramide
    • Drug: Ketorolac
    • Drug: Dexamethasone
    • Drug: Benadryl
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 16, 2018)
80
Original Estimated Enrollment  ICMJE
 (submitted: March 10, 2017)
60
Actual Study Completion Date  ICMJE October 2017
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Chief compliant of a benign, non-life threatening headache that the PI/AI believe will require parental analgesia for management.
  2. Ability to comprehend, speak, read, and write in the English language

Exclusion Criteria:

  1. Age less than 18 and greater than 65
  2. History of hypersensitivity to Ketamine, diphenhydramine, metoclopramide, ketorolac or dexamethasone
  3. Weight less than 45 kg or more than 115 kg
  4. Pregnancy or lactating female.
  5. Patient is female of child-bearing age and unwilling to provide urine or blood for HCG analysis
  6. Altered mental, diminished decision making capacity
  7. Poor vital sign stability Hypoxia: O2 < 92%, Hypotension: SBP< 80 Hypertension: SBP>220 Heart rate: < 50 or >150 Respiratory Rate: <8 or >30
  8. Presence of chronic oxygen-dependent pulmonary disease, liver cirrhosis, or renal disease requiring dialysis
  9. Presence of ischemic heart disease, heart failure, or a history of unstable dysrhythmias
  10. History of schizophrenia, psychosis or hallucinations (as assessed by electronic chart review)
  11. History of alcohol or drug abuse
  12. History of intracranial hypertension
  13. History of glaucoma
  14. History of HIV or immunosuppression
  15. Presence of intracranial mass or vascular lesion (defined as inclusion criteria 1. As benign headaches)
  16. Poorly controlled thyroid disease
  17. Concomitant infections
  18. History of pheochromocytoma
  19. History of epilepsy
  20. History of active bleeding or those receiving anticoagulants.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03081416
Other Study ID Numbers  ICMJE C.2016.072
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Danny Villalobos, Brooke Army Medical Center
Study Sponsor  ICMJE Brooke Army Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Brooke Army Medical Center
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP