N-acetylcysteine for Post-Hysterectomy Pain

Overseen By Haley Nitchie, MHA

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Medical University of South Carolina

Must not be taking: Inhaled bronchodilators

Disqualifiers: Asthma, Diabetes, Blood clotting, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

240 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug N-acetylcysteine for post-hysterectomy pain?

Research suggests that N-acetylcysteine (NAC) may help reduce pain and inflammation, as seen in studies on endometriosis-related pain. This indicates potential benefits for managing post-hysterectomy pain, although direct evidence for this specific use is not provided. ^{1 2 3 4 5}

Is N-acetylcysteine generally safe for humans?

N-acetylcysteine (NAC) is generally considered safe for humans and has been used for various medical conditions, including as an antidote for acetaminophen overdose and to protect against kidney injury from contrast media. It has been studied for its antioxidant properties and potential benefits in conditions like respiratory illnesses, heart disease, and heavy metal poisoning, with no significant undesired side effects reported. ^{2 6 7 8 9}

How is the drug N-acetylcysteine unique for post-hysterectomy pain?

N-acetylcysteine (NAC) is unique because it has antioxidant properties that may help reduce inflammation and pain, which is different from typical pain medications. It is also used in various other conditions like liver protection and endometriosis-related pain, suggesting its potential versatility in managing post-surgical pain. ^{1 5 10 11 12}

What is the purpose of this trial?

This study will enroll females who are ages 18 and older undergoing a laparoscopic or robotic, partial or full hysterectomy. Participants will be randomized to receive IV n-acetylcysteine or placebo during the first 60 minutes of their procedure. At various time points after the procedure patients will be asked to report their pain scores, and any pain medication taken.

Research Team

Sylvia Wilson, MD

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

This trial is for women aged 18 or older who are having a laparoscopic or robotic hysterectomy. They must be able to give informed consent and speak English. It's not for those with a bad reaction to acetylcysteine, active asthma, under 40kg in weight, or insulin-dependent diabetes needing D5W.

Inclusion Criteria

I'm sorry, but I need more context or specific information to help rewrite the exclusion criterion.

"Inclusion" refers to the specific requirements that a person must meet in order to be eligible to participate in a clinical trial. These requirements can include age, gender, medical history, and other factors.

I need insulin and D5W for my diabetes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IV n-acetylcysteine or placebo during the first 60 minutes of their hysterectomy procedure

1 day

1 visit (in-person)

Postoperative Monitoring

Participants report pain scores and opioid consumption is measured for 72 hours post-medication

3 days

Daily monitoring (virtual or in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including PACU opioid consumption and non-opioid analgesic administration

up to 52 weeks

Treatment Details

Interventions

• IV N-acetylcysteine
• IV Placebo
• Laparoscopic or Robotic Hysterectomy
• Partial or Full Hysterectomy

Trial Overview The study tests if IV N-acetylcysteine can reduce pain and opioid use after a hysterectomy compared to an IV placebo. Participants will randomly receive one of the treatments during surgery and report their pain levels and medication use afterward.

Participant Groups

Group I: IV N-acetylcysteine Active Control 1 Intervention

Patients will receive: N-acetylcysteine (NAC) 150 mg/kg (Max dose 15,000 mg) through an IV that will run for 60 minutes at the start of the procedure.

Group II: IV Placebo Placebo Group 1 Intervention

Patients will receive: Placebo 0 mg/kg (placebo: 0.45% NaCl or D5W) through an IV that will run for 60 minutes at the start of the procedure.

Laparoscopic or Robotic Hysterectomy is already approved in United States, European Union for the following indications:

Approved in United States as Acetadote for:

• acetaminophen overdose
• mucolytic therapy

Approved in European Union as Fluimucil for:

• mucolytic therapy
• respiratory tract diseases

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Findings from Research

A review of three studies, including two randomized controlled trials, found no significant difference in complication rates between patients receiving N-acetylcysteine (NAC) and those who did not after liver resection surgery.

Some studies indicated potential safety concerns with NAC, such as a higher incidence of post-hepatectomy liver failure and delirium, suggesting that routine use of NAC in this context is not supported by current evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current evidence for the use of N-acetylcysteine following liver resection. Kemp, R., Mole, J., Gomez, D.[2019]

N-acetyl-L-cysteine (NAC) reduces the proliferation of endometrial cells and promotes a less invasive and less inflammatory state, which could be beneficial for treating endometriosis.

NAC has no undesired side effects, including maintaining fertility potential, making it a promising option for clinical treatment of endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

More than antioxidant: N-acetyl-L-cysteine in a murine model of endometriosis. Pittaluga, E., Costa, G., Krasnowska, E., et al.[2013]

N-acetylcysteine (NAC) has shown promise in experimental models of liver ischaemia-reperfusion (I/R) injury, particularly in reducing liver damage and improving bile production when administered before ischaemia, with 15 out of 19 studies reporting positive outcomes.

However, clinical studies in liver transplantation indicate only a modest improvement in liver enzyme levels, with no significant benefits observed in patient or graft survival, suggesting that while NAC may help in experimental settings, its clinical efficacy remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental and clinical evidence for modification of hepatic ischaemia-reperfusion injury by N-acetylcysteine during major liver surgery. Jegatheeswaran, S., Siriwardena, AK.[2022]

In a study of 64 patients treated with intravenous acetylcysteine for acetaminophen toxicity, the treatment was found to be safe and effective, with only 6% of patients experiencing death and 3% requiring liver transplants.

Patients who received intravenous acetylcysteine within 8 hours of acetaminophen ingestion had significantly better outcomes, with no deaths or liver failure, and a shorter hospital stay compared to those treated later.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of acetadote for acetaminophen toxicity. Whyte, AJ., Kehrl, T., Brooks, DE., et al.[2013]

In a study of 120 patients with endometriosis, oral N-acetylcysteine (NAC) significantly reduced pain symptoms such as dysmenorrhea, dyspareunia, and chronic pelvic pain, as well as the size of ovarian endometriomas after 3 months of treatment.

NAC also lowered serum levels of Ca125 and showed potential in improving fertility, with 39 out of 52 patients desiring pregnancy successfully achieving it within 6 months of starting therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of N-Acetylcysteine on Endometriosis-Related Pain, Size Reduction of Ovarian Endometriomas, and Fertility Outcomes. Anastasi, E., Scaramuzzino, S., Viscardi, MF., et al.[2023]

N-acetylcysteine significantly reversed reproductive toxicity caused by perfluorooctanoic acid in male Wistar rats, improving sperm motility, count, and viability after 28 days of treatment.

The treatment also reduced oxidative stress and inflammation in the testes and epididymis, indicating that N-acetylcysteine can enhance reproductive function by mitigating the harmful effects of environmental toxins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetyl cysteine co-treatment abates perfluorooctanoic acid-induced reproductive toxicity in male rats. Owumi, SE., Akomolafe, AP., Imosemi, IO., et al.[2021]

N-acetylcysteine (NAC) is effective in promoting the synthesis of glutathione (GSH), which helps detoxify the body and combat oxidative stress, making it beneficial for conditions like HIV, cancer, and heart disease.

NAC is the primary treatment for acetaminophen-induced liver damage and also serves as a chelating agent for acute heavy metal poisoning, protecting organs and aiding in metal elimination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of N-acetylcysteine. Kelly, GS.[2013]

N-acetylcysteine (NAC) is a versatile compound that serves as a precursor to important antioxidants and has been used historically for treating respiratory issues and acetaminophen overdose.

Recent studies suggest that NAC may have therapeutic potential in a variety of conditions, including cancer, heart disease, and HIV, due to its strong antioxidant properties that combat free radical damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine. [2013]

Contrast-induced acute kidney injury (CI-AKI) is a significant cause of hospital-acquired renal failure, affecting about 10% of cases and leading to longer hospital stays and worse patient outcomes.

N-acetylcysteine (NAC) is a promising treatment due to its antioxidant properties, which may help prevent CI-AKI by scavenging harmful free radicals, although the study will further explore its effectiveness through experimental and clinical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nephrotoxicity of contrast media and protective effects of acetylcysteine. Briguori, C., Quintavalle, C., De Micco, F., et al.[2022]

N-acetylcysteine is an effective antidote for paracetamol (acetaminophen) overdose, particularly when given within eight hours of ingestion.

It can be administered either intravenously or orally, and it has minimal side effects, making it a safe option for treating paracetamol intoxication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paracetamol intoxication and N-acetyl-cysteine treatment. De Groote, J., Van Steenbergen, W.[2016]

N-acetylcysteine (NAC) did not show a significant difference in overall survival rates compared to placebo in patients with non-paracetamol drug-induced liver injury, with survival rates of 70% for NAC and 66% for placebo after 3 weeks.

However, NAC improved transplant-free survival rates, with 40% of patients receiving NAC surviving without a transplant compared to 27% in the placebo group, indicating potential benefits in specific cases of non-paracetamol DILI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine for non-paracetamol drug-induced liver injury: a systematic review. Chughlay, MF., Kramer, N., Spearman, CW., et al.[2021]

N-acetylcysteine (NAC) has a wide range of clinical applications, including treatment for paracetamol overdose and various disorders, due to its antioxidative properties and ability to restore impaired cellular components.

NAC's unique effectiveness is likely due to its ability to reduce disulfide bonds in proteins, which alters their structure and function, although more research is needed to fully understand its mechanisms and how it interacts with cell signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The chemistry and biological activities of N-acetylcysteine. Samuni, Y., Goldstein, S., Dean, OM., et al.[2022]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Current evidence for the use of N-acetylcysteine following liver resection. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

More than antioxidant: N-acetyl-L-cysteine in a murine model of endometriosis. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Experimental and clinical evidence for modification of hepatic ischaemia-reperfusion injury by N-acetylcysteine during major liver surgery. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of acetadote for acetaminophen toxicity. [2013]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of N-Acetylcysteine on Endometriosis-Related Pain, Size Reduction of Ovarian Endometriomas, and Fertility Outcomes. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

N-acetyl cysteine co-treatment abates perfluorooctanoic acid-induced reproductive toxicity in male rats. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Clinical applications of N-acetylcysteine. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

N-acetylcysteine. [2013]

9. Germany pubmed.ncbi.nlm.nih.gov

Nephrotoxicity of contrast media and protective effects of acetylcysteine. [2022]

10. Belgium pubmed.ncbi.nlm.nih.gov

Paracetamol intoxication and N-acetyl-cysteine treatment. [2016]

11. England pubmed.ncbi.nlm.nih.gov

N-acetylcysteine for non-paracetamol drug-induced liver injury: a systematic review. [2021]

12. Netherlands pubmed.ncbi.nlm.nih.gov

The chemistry and biological activities of N-acetylcysteine. [2022]