Ketamine Analgesia in Third Molar Surgery

NCT ID: NCT04459377

Last Updated: 2022-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-14
• Study Completion Date: 2022-09-30

Brief Summary

BACKGROUND AND PURPOSE Outpatient surgery (day case surgery) is increasing. When the patients go home on the same day, this demands safe pain relief. A reduction of morphine (opioid) use is sought because of side effects and the dependency risk. An effective alternative to opioids is ketamine, which lacks the side effects of opioids but provides powerful analgesic effects.

METHOD At the start of surgery, Ketamine or placebo will be given in a vein to evaluate if the acute pain decreases significantly. Inflammation is known to cause pain. By measuring different proteins in the blood, the investigators want to understand how inflammation links to the pain. Wisdom tooth surgery provides significant post-operative pain and is a widely accepted pain model in drug studies. Patients referred for wisdom tooth surgery are asked to participate in the study. For statistical certainty, in total 165 persons will be enrolled to three groups. Two with active drug (different dose) and one placebo. Everyone gets local anesthesia. The completion of the study will be done in four years. The Ethics Review Board has approved the study.

CLINICAL RELEVANCE Effective pain relief after daily surgical procedures is important for patient´s safety and reducing the risk of long-term pain. It is also ethically necessary for the continued expansion of day case surgery. New knowledge of the mechanisms of pain increases the opportunities for individual and safe pain relief. Day case surgery is performed in all operating specialties, this might affects many patients nationally and internationally.

Conditions

Pain; Postoperative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Sodium Chloride solution (9mg / ml) 0.2ml / kg slow intravenous injection (2ml / min).

Group Type: PLACEBO_COMPARATOR

Sodium Chloride 0.9% Inj

Intervention Type: DRUG

Patients are randomized to three groups. Randomization in blocks of six patients stratified by sex. A list of serial numbers and randomized group affiliation is produced which is open to the pharmacy's manufacturing staff and closed to the staff of the trial. The pharmacy prepares filled syringes with investigation drug in accordance with randomized group affiliation.

All groups are sedated with midazolam intravenously to a defined end point. A syringe pump with volume accuracy ± 2% injects the test drug (P, K1 or K2). One infusion set is coupled between the syringe and a three-way connection, which in turn is connected to a peripheral venous catheter (PVK). This PVK is also used for blood sampling. Blood is sampled at two occasions. Directly preoperatively and two hours after surgery. The third molar is surgically removed.

K1

S-Ketamine (0.125 mg / kg body weight). (0.625mg / ml x 0.2ml / kg) slow intravenous injection (2ml / min).

Group Type: ACTIVE_COMPARATOR

S-Ketamine

Intervention Type: DRUG

Patients are randomized to three groups. Randomization in blocks of six patients stratified by sex. A list of serial numbers and randomized group affiliation is produced which is open to the pharmacy's manufacturing staff and closed to the staff of the trial. The pharmacy prepares filled syringes with investigation drug in accordance with randomized group affiliation.

All groups are sedated with midazolam intravenously to a defined end point. A syringe pump with volume accuracy ± 2% injects the test drug (P, K1 or K2). One infusion set is coupled between the syringe and a three-way connection, which in turn is connected to a peripheral venous catheter (PVK). This PVK is also used for blood sampling. Blood is sampled at two occasions. Directly preoperatively and two hours after surgery. The third molar is surgically removed.

K2

S-Ketamine (0.25 mg / kg body weight). (1.25mg / ml x 0.2ml / kg) slow intravenous injection (2ml / min).

Group Type: ACTIVE_COMPARATOR

S-Ketamine

Intervention Type: DRUG

Patients are randomized to three groups. Randomization in blocks of six patients stratified by sex. A list of serial numbers and randomized group affiliation is produced which is open to the pharmacy's manufacturing staff and closed to the staff of the trial. The pharmacy prepares filled syringes with investigation drug in accordance with randomized group affiliation.

All groups are sedated with midazolam intravenously to a defined end point. A syringe pump with volume accuracy ± 2% injects the test drug (P, K1 or K2). One infusion set is coupled between the syringe and a three-way connection, which in turn is connected to a peripheral venous catheter (PVK). This PVK is also used for blood sampling. Blood is sampled at two occasions. Directly preoperatively and two hours after surgery. The third molar is surgically removed.

Interventions

S-Ketamine

Patients are randomized to three groups. Randomization in blocks of six patients stratified by sex. A list of serial numbers and randomized group affiliation is produced which is open to the pharmacy's manufacturing staff and closed to the staff of the trial. The pharmacy prepares filled syringes with investigation drug in accordance with randomized group affiliation.

All groups are sedated with midazolam intravenously to a defined end point. A syringe pump with volume accuracy ± 2% injects the test drug (P, K1 or K2). One infusion set is coupled between the syringe and a three-way connection, which in turn is connected to a peripheral venous catheter (PVK). This PVK is also used for blood sampling. Blood is sampled at two occasions. Directly preoperatively and two hours after surgery. The third molar is surgically removed.

Intervention Type: DRUG

Sodium Chloride 0.9% Inj

Patients are randomized to three groups. Randomization in blocks of six patients stratified by sex. A list of serial numbers and randomized group affiliation is produced which is open to the pharmacy's manufacturing staff and closed to the staff of the trial. The pharmacy prepares filled syringes with investigation drug in accordance with randomized group affiliation.

All groups are sedated with midazolam intravenously to a defined end point. A syringe pump with volume accuracy ± 2% injects the test drug (P, K1 or K2). One infusion set is coupled between the syringe and a three-way connection, which in turn is connected to a peripheral venous catheter (PVK). This PVK is also used for blood sampling. Blood is sampled at two occasions. Directly preoperatively and two hours after surgery. The third molar is surgically removed.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy or mild well-compensated systemic disease (ASA I & II)
• 18- <45 years
• 50-100 kg body weight

Exclusion Criteria

• Medication drugs: analgesics, hypnotics (the last week before surgery), thyroid hormones, psychoactive drugs or monoamine oxidase inhibitors (MAO inhibitors).
• Hypertension [> 150/95 mmHg in screening study]
• Heart failure
• Psychosis
• Epilepsy
• Hyperthyreosis
• Myasthenia gravis
• Glaucoma
• Verified sleep apnea
• Diabetes (insulin treated)
• Porphyria
• Pregnancy
• Breast-feeding
• Blood transmitted infections, such as HIV and hepatitis B and C
• Known hypersensitivity to midazolam, ketamine, ibuprofen, or local anesthetics
• Inability to obtain the requisite written or oral information

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 44 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Uppsala University

OTHER

Sponsor Role: collaborator

Center for Clinical Research Dalarna, Sweden

OTHER

Sponsor Role: collaborator

Dalarna County Council, Sweden

OTHER

Sponsor Role: lead

Responsible Party

Lars Eriksson

Senior Consultant in Oral and Maxillofacial Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lars Sand, Professor, DDS, MD

Role: STUDY_DIRECTOR

Uppsala University

Locations

Käkkirurgiska kliniken, Falu lasarett

Falun, Dalarna County, Sweden

Countries

Sweden

Other Identifiers

2014-004235-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20140929sketamine

Identifier Type: -

Identifier Source: org_study_id