Inhaled Nebulised S(+)-Ketamine for Postoperative Analgesia

NCT02397356 | Withdrawn Phase 4

• 2 other identifiers: R14066M2014-000837-22
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Ketamine has been administrated via the intravenous, intramuscular, subcutaneous, rectal, oral, transdermal, intranasal, sublingual, transmucosal, epidural, intrathecal, and intra-articular routes. Pharmacokinetic properties of inhaled ketamine have not been studied officially, but one of the investigators researchers has tested nebulized ketamine on himself with repeated painful stimulus and monitoring applied. Based on this experiment, analgesic effect is roughly estimated to begin in 3 minutes.Ketamine has been used successfully to treat acute pain in intranasal form. The primary purpose of this study is to evaluate whether nebulised S(+)-ketamine carries potential as a an analgesic bypassing first pass metabolism and without the need for intravenous access. Secondary aim is to assess the duration of analgesia obtained by nebulized S-ketamine. Thirdly, the aim is to evaluate whether inhaled nebulized ketamine decreases the need for rescue analgesia during PACU care. The subjects are recruited among patients coming in for a surgical intervention (orthopedic, gastrointestinal, plastic or urologic surgery) and needing further observation in postoperative care unit (PACU). It was calculated that sample size of 8 subjects per group would be required to achieve statistical power of 80% and detect a difference of 3 units in NRS-values with standard deviation of 2 units and type I error of 5%. To prepare for possible dropouts, total of 20 subjects will be recruited (10 in each group). Patients will receive either nebulized placebo (i.e. saline) or ketamine (Ketanest-S) when they require pain alleviation in the PACU. Dosage of ketamine is 1 mg/kg. Patients will be randomized into two groups so that other group's first inhalation contains ketamine and second inhalation placebo and in the opposite order.

Conditions

Pain, Postoperative

Keywords

ketamine

Outcome Measures

Primary Outcomes (1)

• Potential of S(+)-ketamine as an analgesic in the nebulised form

  TIme measured for the second request of analgesia. 3 minutes is the anticipated duration of analgesia achieved by nebulised s-ketamine.

  3 minutes

Secondary Outcomes (2)

• Duration of analgesia

  10 minutes

• Duration of need for PACU care

  3 hours

Study Arms (2)

Ketamine first AB

EXPERIMENTAL

Patients in this group will first receive a dose of ketamine in the nebulised form when they ask for pain relief. The second time they ask for pain relief, they will receive physiological salt in the nebulised form.

Drug: Ketamine first AB; Drug: Placebo first BA

Placebo first BA

ACTIVE COMPARATOR

Patients in this group will first receive physiological salt in the nebulised form form when they ask for pain relief. The second time they ask for pain relief, they will receive a dose of ketamine in the nebulised.

Drug: Ketamine first AB; Drug: Placebo first BA

Interventions

Ketamine first AB DRUG

Nebulised ketamine 1mg/kg

Also known as: S(+)-ketamine

Ketamine first AB; Placebo first BA

Placebo first BA DRUG

Nebulised saline 1-2ml

Also known as: NaCl, Saline

Ketamine first AB; Placebo first BA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• male
• years of age
• PACU care after general anesthesia

You may not qualify if:

• female
• asthma
• COPD
• diabetes mellitus
• unstable angina pectoris
• high intracranial pressure
• elevated intraocular pressure
• neurosurgery
• epidural or spinal analgesia
• history of long-term pain state
• poor co-operation

Sponsors & Collaborators

• Tampere University Hospital: lead

Study Sites (1)

Tampere University Hospital

Tampere, 3351, Finland

Location

Related Publications (13)

• Clements JA, Nimmo WS. Pharmacokinetics and analgesic effect of ketamine in man. Br J Anaesth. 1981 Jan;53(1):27-30. doi: 10.1093/bja/53.1.27.

  PMID: 7459184 BACKGROUND

• DOMINO EF, CHODOFF P, CORSSEN G. PHARMACOLOGIC EFFECTS OF CI-581, A NEW DISSOCIATIVE ANESTHETIC, IN MAN. Clin Pharmacol Ther. 1965 May-Jun;6:279-91. doi: 10.1002/cpt196563279. No abstract available.

  PMID: 14296024 BACKGROUND

• Craven R. Ketamine. Anaesthesia. 2007 Dec;62 Suppl 1:48-53. doi: 10.1111/j.1365-2044.2007.05298.x.

  PMID: 17937714 BACKGROUND

• Aan Het Rot M, Zarate CA Jr, Charney DS, Mathew SJ. Ketamine for depression: where do we go from here? Biol Psychiatry. 2012 Oct 1;72(7):537-47. doi: 10.1016/j.biopsych.2012.05.003. Epub 2012 Jun 16.

  PMID: 22705040 BACKGROUND

• Aroni F, Iacovidou N, Dontas I, Pourzitaki C, Xanthos T. Pharmacological aspects and potential new clinical applications of ketamine: reevaluation of an old drug. J Clin Pharmacol. 2009 Aug;49(8):957-64. doi: 10.1177/0091270009337941. Epub 2009 Jun 22.

  PMID: 19546251 BACKGROUND

• Klepstad P, Maurset A, Moberg ER, Oye I. Evidence of a role for NMDA receptors in pain perception. Eur J Pharmacol. 1990 Oct 23;187(3):513-8. doi: 10.1016/0014-2999(90)90379-k.

  PMID: 1963598 BACKGROUND

• Arendt-Nielsen L, Nielsen J, Petersen-Felix S, Schnider TW, Zbinden AM. Effect of racemic mixture and the (S+)-isomer of ketamine on temporal and spatial summation of pain. Br J Anaesth. 1996 Nov;77(5):625-31. doi: 10.1093/bja/77.5.625.

  PMID: 8957979 BACKGROUND

• Dal D, Celebi N, Elvan EG, Celiker V, Aypar U. The efficacy of intravenous or peritonsillar infiltration of ketamine for postoperative pain relief in children following adenotonsillectomy. Paediatr Anaesth. 2007 Mar;17(3):263-9. doi: 10.1111/j.1460-9592.2006.02095.x.

  PMID: 17263742 BACKGROUND

• Chong C, Schug SA, Page-Sharp M, Jenkins B, Ilett KF. Development of a sublingual/oral formulation of ketamine for use in neuropathic pain: Preliminary findings from a three-way randomized, crossover study. Clin Drug Investig. 2009;29(5):317-24. doi: 10.2165/00044011-200929050-00004.

  PMID: 19366273 BACKGROUND

• Christensen K, Rogers E, Green GA, et al. Safety and efficacy of intranasal ketamine for acute postoperative pain. Acute Pain. 2007;9(4):183-192.

  BACKGROUND

• Zhu MM, Zhou QH, Zhu MH, Rong HB, Xu YM, Qian YN, Fu CZ. Effects of nebulized ketamine on allergen-induced airway hyperresponsiveness and inflammation in actively sensitized Brown-Norway rats. J Inflamm (Lond). 2007 May 4;4:10. doi: 10.1186/1476-9255-4-10.

  PMID: 17480224 BACKGROUND

• Johansson J, Sjoberg J, Nordgren M, Sandstrom E, Sjoberg F, Zetterstrom H. Prehospital analgesia using nasal administration of S-ketamine--a case series. Scand J Trauma Resusc Emerg Med. 2013 May 14;21:38. doi: 10.1186/1757-7241-21-38.

  PMID: 23672762 BACKGROUND

• European Medicines Agency. Guideline for good clinical practice 2002. www.ema.com.eu. Accessed 8/1, 2012.

  BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Ketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Antti Kämäräinen, MD, PhD

  Pirkanmaa District Hospital, Department of Emergency Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2014
• First Posted: March 24, 2015
• Study Start: August 1, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: August 28, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)