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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether N-acetylcysteine, a medication, can reduce pain after a hysterectomy, a surgery to remove part or all of the uterus. Participants will receive either the actual treatment or a placebo (a harmless pill or solution with no active ingredients) during the first hour of their surgery. Researchers will then ask participants to report their pain levels and any pain medication they take afterward. Women undergoing a planned laparoscopic or robotic hysterectomy might find this trial relevant. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in pain management.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that N-acetylcysteine (NAC) is generally safe for use. As an FDA-approved drug, it has passed safety tests for other applications. NAC is derived from an amino acid, a fundamental component of proteins in the body. Studies suggest that NAC might help reduce pain and the need for pain medication after surgery.

Most people tolerate NAC well, even at high doses. Mild side effects, such as an upset stomach, can occur but are uncommon. Previous research has used NAC in various surgical settings to manage pain, showing promise in reducing the need for opioids after surgery. Overall, evidence supports NAC as a safe option for many individuals. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for post-hysterectomy pain?

Unlike the standard pain management options for post-hysterectomy, which often include opioids and NSAIDs, N-acetylcysteine (NAC) offers a novel approach. Researchers are excited about NAC because it acts as an antioxidant, which may help reduce inflammation and pain differently than traditional pain relievers. This new mechanism of action could potentially minimize the need for opioids, reducing the risk of addiction and side effects. Additionally, NAC is administered intravenously at the start of the procedure, offering a straightforward delivery method that integrates seamlessly into surgical care.

What evidence suggests that IV N-acetylcysteine might be an effective treatment for post-hysterectomy pain?

Studies have shown that N-acetylcysteine (NAC) can help reduce pain after surgery. In this trial, some participants will receive NAC, while others will receive a placebo. Research indicates that patients who took NAC reported feeling less pain and needed fewer painkillers compared to those who took a placebo, a harmless solution with no active ingredients. NAC reduces swelling, which might explain its effectiveness in pain relief. This reduction in pain can be especially helpful after surgeries like hysterectomies. These findings suggest NAC could be a promising option for managing post-surgical pain. ^{1 6 7 8 9}

Who Is on the Research Team?

Sylvia Wilson, MD

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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 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) 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]

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 (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]

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-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-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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06039566

NAC Vs Placebo on Opioid Use for Hysterectomy | ... Using a Visual Analog Scale from 0-100, patients will report pain scores from 0-72 hours post-medication. A lower pain score means a better outcome. Study ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11486111/

Perioperative N-acetylcysteine: evidence and indications N-acetylcysteine (NAC), the treatment of acetaminophen overdose, decreased inflammation and has other positive effects on the body that may help pain after ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11432659/

Multimodal Analgesia and Outcomes in Hysterectomy Surgery ... Objective: We aimed to investigate the impact of multimodal analgesia on postoperative complications and opioid prescription on a national ...

4. doctorize.com doctorize.com/resources/news/the-promising-role-of-n-acetylcysteine-in-pain-management-and-opioid-reduction-post-surgery/

The Promising Role of N Acetylcysteine in Pain ... Patients who received NAC reported lower pain scores and required fewer opioids post-surgery compared to those who received a placebo. This ...

5. researchgate.net researchgate.net/publication/224830430_Postoperative_Pain_Management_After_Hysterectomy_A_Simple_Approach

Postoperative Pain Management After Hysterectomy A ... The effectiveness of acute pain services in 14 hospitals in one English region was audited. We collected data on analgesia used, its efficacy ...

6. webmd.com webmd.com/vitamins/ai/ingredientmono-1018/n-acetyl-cysteine-nac

N-Acetyl Cysteine (Nac) – Uses, Side Effects, and More N-acetyl cysteine (NAC) comes from the amino acid L-cysteine. Amino acids are building blocks of proteins. NAC has many uses and is an FDA approved drug.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34446544/

Postoperative pain reduction by pre-emptive N-acetylcysteine We investigated whether pre-emptive administration of N-acetylcysteine leads to a reduction in postoperative pain after laparoscopic inguinal hernia repair.

8. web.musc.edu web.musc.edu/about/news-center/2024/01/12/nac-for-surgical-pain

Could an already approved drug cut down on opioid use ... MUSC pilot study shows that an FDA-approved drug called NAC could be useful for reducing the need for opioids after spinal surgery.

9. aafp.org aafp.org/pubs/afp/issues/2009/0801/p265.html

N-Acetylcysteine: Multiple Clinical Applications At dosages of 1,200 mg twice daily or lower, N-acetylcysteine is well tolerated. At these dosages, side effects are unusual, but may include ...