Ketamine for Hemorrhoids

Recruiting at 1 trial location

Overseen By Theresa J Lander

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Oklahoma

Must not be taking: Narcotics

Disqualifiers: Schizophrenia, Psychosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether ketamine, a medication often used for pain relief and sedation, can aid recovery in patients undergoing surgery for severe hemorrhoids. Researchers aim to determine if ketamine eases recovery compared to standard treatment alone. Participants will be randomly assigned to receive either ketamine or the usual anesthesia during surgery, without knowing which they received. This trial targets individuals undergoing surgery for Grade III or IV hemorrhoids, which are severe and impact daily life. As a Phase 4 trial, this research seeks to understand how ketamine, an FDA-approved and effective treatment, can benefit more patients undergoing hemorrhoid surgery.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are using narcotics regularly, you must stop at least one month before the hemorrhoidectomy.

What is the safety track record for ketamine?

Research has shown that ketamine is usually safe for use during surgeries. In studies involving hemorrhoid surgery, patients did not experience major side effects from ketamine. One study with 83 patients found that adding ketamine to anesthesia did not increase complications compared to not using it.

Another study suggested that ketamine might help reduce long-term pain after surgery, but the evidence remains weak, requiring further research. Since ketamine is often used during surgeries to manage pain, it is known to be safe. Most patients tolerate it well, experiencing few serious side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard hemorrhoid treatments, which primarily involve topical creams, suppositories, or surgical removal, ketamine is unique because it is administered intravenously during surgery. This approach not only utilizes ketamine's anesthetic properties but also explores its potential anti-inflammatory effects, which could offer faster relief and improved post-surgical recovery. Researchers are excited about this treatment because ketamine works on the central nervous system differently than traditional anesthetics and pain relievers, potentially reducing the need for opioids post-surgery and minimizing side effects associated with conventional treatments.

What evidence suggests that ketamine might be an effective treatment for hemorrhoids?

Research shows that ketamine can help reduce pain during surgery. In this trial, participants in the intraoperative ketamine infusion arm will receive ketamine to assess its effectiveness in managing pain during hemorrhoid surgery. Earlier studies found ketamine effectively blocks pain during operations, which is crucial for hemorrhoid surgery where pain management is vital. Experts agree that ketamine is a promising option for reducing pain after hemorrhoid surgery. By blocking pain signals, it may help patients recover more comfortably after the procedure. ^{2 6 7 8 9}

Who Is on the Research Team?

Steven Carter, MD

Principal Investigator

University of Oklahoma

Are You a Good Fit for This Trial?

This trial is for adults aged 18-100 who are having surgery (hemorrhoidectomy) for severe hemorrhoids (Grade III or IV). They must be able to have general anesthesia and not use strong painkillers regularly. People with a history of schizophrenia, other hallucinatory psychiatric illnesses, or psychosis cannot participate.

Inclusion Criteria

Adults aged 18-100

You recently had surgery to remove severe hemorrhoids (Grade III or IV).

Exclusion Criteria

Inability to undergo general anesthesia

Chronic narcotic usage defined as either having a pain contract with a pain management specialist and no narcotic usage for one month prior to hemorrhoidectomy.

You have medical conditions that make it unsafe for you to have a hemorrhoidectomy (surgical removal of hemorrhoids).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo hemorrhoidectomy with either intraoperative ketamine infusion or standard anesthesia

1 day

1 visit (in-person, surgery)

Post-operative Monitoring

Participants' post-operative pain is assessed using a numeric rating scale and the Wong-Baker FACES pain scale

2 weeks

1 visit (in-person), multiple contacts (phone)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of narcotic usage

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine

Trial Overview The study is testing if ketamine can help with pain after hemorrhoid surgery. About 100 patients will either receive ketamine or no ketamine while under anesthesia, without knowing which group they're in; however, the researchers will know.

How Is the Trial Designed?

Group I: Intraoperative ketamine infusion Active Control 1 Intervention

Subjects in this group will receive standard anesthesia during surgery and a dose of ketamine at 0.3 mg/kg IV bolus prior to surgical incision. If the procedure lasts more than 1 hour, an additional bolus dose will be given.

Group II: Control group Active Control 1 Intervention

This group will only receive the standard anesthesia during surgery with no ketamine.

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Published Research Related to This Trial

A new subcutaneous formulation of ketamine was developed using Captisol® to achieve a balanced pH and osmolality close to physiological levels, which may reduce injection site irritation and sterile abscesses commonly seen with current formulations.

This innovative formulation strategy allows for a buffered ketamine solution that maintains high concentration while minimizing adverse reactions, suggesting potential for broader application in other amine-based medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three Birds, One Excipient: Development of an Improved pH, Isotonic, and Buffered Ketamine Formulation for Subcutaneous Injection. Wallach, J., Gamrat, J., Jauhola-Straight, R., et al.[2022]

Ketamine use more than three times a week is linked to lower bladder function, as indicated by reduced voided volumes and higher scores on the Pelvic Pain, Urgency and Frequency questionnaire, especially in users with over 24 months of use.

After one year of abstinence from ketamine, individuals showed significant improvements in bladder function, with lower symptom scores and higher voided volumes, suggesting that some urinary tract changes may be reversible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower urinary tract changes in young adults using ketamine. Mak, SK., Chan, MT., Bower, WF., et al.[2022]

In a study involving 18 cats, it was found that administering xylazine before ketamine significantly prolonged the duration of anesthesia and increased the plasma half-life of ketamine, indicating a potential for enhanced sedation effects.

Xylazine also delayed the production of norketamine, the primary metabolite of ketamine, suggesting that the combination of these drugs could alter the metabolism and effectiveness of ketamine in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of premedication with xylazine on the distribution and metabolism of intramuscularly administered ketamine in cats. Waterman, AE.[2016]

A study involving 12 children aged 1 year 7 months to 6 years found that a ketamine lollipop (50 mg) was well-tolerated, with participants showing a relatively good emotional state during premedication.

The results indicate that ketamine lollipops could be a promising option for premedication in pediatric patients, as they did not exhibit typical side effects associated with ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ketamine lollipop for pediatric premedication]. Horiuchi, T., Kurehara, K., Kitaguchi, K., et al.[2013]

A review of 41 treatment arms from 21 studies found that ketamine formulations that maximize first pass metabolism and delay the time to peak concentration (Tmax) are associated with better safety and tolerability, particularly in reducing side effects like dissociation and increased blood pressure.

The study revealed strong correlations between the ketamine:norketamine ratio and both dissociation ratings and blood pressure changes, suggesting that careful formulation can help minimize adverse effects while maintaining the antidepressant efficacy of ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. Glue, P., Russell, B., Medlicott, NJ.[2021]

Chronic use of ketamine can lead to serious health issues, including biliary duct damage (cholangiopathy) and bladder dysfunction (ulcerative cystitis), which are becoming more recognized in medical settings.

A case report of a teenage patient illustrates the rare occurrence of both conditions occurring simultaneously, highlighting the need for increased awareness among emergency physicians as recreational ketamine use rises.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recreational ketamine-induced cholangiopathy and ulcerative cystitis. Vu, DM., Freyre, K., Opsha, O., et al.[2021]

Adding ketamine to caudal local anaesthetics significantly prolongs the time before children need their first pain relief after surgery, with an average increase of 5.60 hours compared to local anaesthetics alone, based on a review of 13 randomized controlled trials involving 584 patients.

While ketamine reduces the need for additional pain relief (rescue analgesia), concerns about potential neurotoxicity and the appropriate dosing in children remain, indicating that further research is needed before widespread clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and adverse effects of ketamine as an additive for paediatric caudal anaesthesia: a quantitative systematic review of randomized controlled trials. Schnabel, A., Poepping, DM., Kranke, P., et al.[2022]

There is currently no standardized safety monitoring protocol for off-label use of generic ketamine, and safety monitoring for intranasal esketamine varies by jurisdiction, leading to potential gaps in patient safety.

The Ketamine Side Effect Tool (KSET) is recommended as a comprehensive tool for monitoring both acute and long-term side effects of ketamine and esketamine treatments, addressing the lack of agreed frameworks for safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. Bayes, A., Short, B., Zarate, CA., et al.[2023]

A new oral gel formulation of ketamine was developed to provide an alternative to the bitter-tasting injectable solution, making it easier and more palatable for patients to take.

The gel maintained its effectiveness and stability over 12 weeks, with the release rate of ketamine being adjustable through the addition of flavoring and other additives, which could enhance patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preparing oral dosage form of ketamine in the hospital for simplicity and patient compliance--preparations using agar]. Kaneuchi, M., Kohri, N., Senbongi, K., et al.[2019]

A meta-analysis of 15 studies involving 1697 patients showed that perioperative intravenous ketamine significantly reduces postoperative depression scores, with the most substantial effects observed on the first day after surgery (SMD -0.97).

While ketamine also decreased pain scores on the first postoperative day, it was associated with a higher risk of adverse effects, including nausea, vomiting, headaches, hallucinations, and dizziness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies. Guo, J., Qiu, D., Gu, HW., et al.[2023]

A 49-year-old woman with severe treatment-resistant major depression experienced significant improvement after receiving 36 sessions of ketamine intravenous therapy over 10 months, resulting in nearly a 50% reduction in her depressive symptoms.

The case suggests that long-term repeated ketamine therapy could be a viable option for patients with treatment-resistant depression, but further research is needed to determine the best treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. Kwon, JH., Sim, WS., Hong, JP., et al.[2018]

Ketamine is recognized for its excellent pain-relieving properties and safety, making it a valuable option for short-term sedation and chronic pain management in children with cancer, although more research is needed to fully establish its efficacy in this area.

Various administration routes for ketamine, including intravenous, intramuscular, and intranasal, have been shown to be effective, and it generally does not lead to significant long-term neurological side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the clinical applications of ketamine in pediatric oncology. Prakash, S., Gupta, AK., Meena, JP., et al.[2021]

In a study of 268 procedures involving 35 children with leukemia, the combination of thiamylal plus pentazocine (TP) provided faster sedation compared to ketamine plus midazolam (KM) during bone marrow aspirations and intrathecal chemotherapy.

While TP was associated with a higher incidence of transient desaturation events, these were manageable with oxygen supplementation, indicating that TP can be a safe and effective alternative for sedation in pediatric oncology procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiamylal Plus Pentazocine Shows Similar Efficacy as Ketamine Plus Midazolam for Painful Procedures in Children With Leukemia. Nakagawa, S., Okamoto, Y., Kodama, Y., et al.[2019]

In a study of 55 children aged 2-6 years, oral transmucosal ketamine (50 mg) was found to be less effective than oral midazolam (0.5 mg/kg) for premedication before minor surgery, as indicated by lower sedation scores and higher rates of agitation.

Children receiving ketamine had more difficulty with separation from parents and showed poorer cooperation with the anesthesia mask compared to those receiving midazolam, suggesting that ketamine may not be a beneficial alternative to midazolam in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of relatively low dose of oral transmucosal ketamine premedication in children: a comparison with oral midazolam. Horiuchi, T., Kawaguchi, M., Kurehara, K., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-4-hemorrhoids-5-2020-31648

Ketamine for Hemorrhoids This trial tests if ketamine can help reduce pain in patients having surgery for severe hemorrhoids. Ketamine is given during the operation to block pain ...

2. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT04248205?keyword=%22Hemorrhoidectomy%22

Ketamine for Post-operative Analgesia in Hemorrhoidectomy This is a prospective, randomized study of ketamine versus no ketamine in approximately 100 patients undergoing hemorrhoidectomy for Grade III or IV hemorrhoids ...

3. journals.lww.com journals.lww.com/ejaintensivecare/fulltext/2023/06000/prospect_guideline_for_haemorrhoid_surgery__a.3.aspx

PROSPECT guideline for haemorrhoid surgery Postoperative pain outcomes (pain scores and analgesic requirements) were the primary outcomes. Other recovery outcomes, including adverse effects, were also ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2780234/

Fast Track Colorectal Surgery - PMC A Cochrane Review has confirmed the efficacy of these devices in a variety of settings including abdominal surgery. Data are not currently available using local ...

5. iris.unil.ch iris.unil.ch/bitstreams/9fab8c4e-8458-46c5-97a6-8b5d9c645b10/download

PROSPECT guideline for haemorrhoid surgery A ... Two trials with 6712 and 82 patients65 investigated the analgesic efficacy of botulinum toxin injection during the procedure, while prescribing ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04248205

Ketamine for Post-operative Analgesia in Hemorrhoidectomy This is a prospective, randomized study of ketamine versus no ketamine in approximately 100 patients undergoing hemorrhoidectomy for Grade III or IV hemorrhoids ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1877886010000030

Effects of perioperative S (+) ketamine infusion added to ... A total of 83 patients scheduled for elective haemorrhoidectomy were randomized to either treatment with placebo or S (+) ketamine. ... safety of S-ketamine ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8415450/

Safety and Effectiveness of Tailored Hemorrhoidectomy in ... Postoperative pain at 30 min, 5 and 10 days after surgery was evaluated using a VAS. Postoperative complications, the number of painkillers used ...

9. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1111/papr.13314

Efficacy and safety of perioperative ketamine for the ... Low-certainty evidence suggests that ketamine compared to placebo may reduce incidence of chronic postsurgical neuropathic pain after 3 months.