Ketorolac for Cleft Lip and Palate

Overseen By Matthew R Greives, MD,MS,FACS

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Syndromic cleft palate, Cardiac malformation, GI complications, Renal disorder, Coagulopathy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate post-operative period (up to 24 hours post-surgery)

74 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding Ketorolac to standard pain treatment can help children with cleft lip and palate eat better after surgery. Participants will receive either Ketorolac or a placebo, a harmless pill with no active ingredients, to compare results. The trial seeks children with a cleft palate, with or without a cleft lip, who have not undergone previous surgery for this condition and do not have certain health issues like heart or digestive problems. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to understand how Ketorolac can further benefit more patients.

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 is the safety track record for Ketorolac?

Research has shown that ketorolac is generally safe after cleft lip and palate surgeries. In a study with 111 patients, a single dose of ketorolac did not cause significant bleeding. Another study found that using ketorolac soon after surgery helped patients leave the hospital sooner and reduced the need for other pain medications. Additionally, ketorolac has been reported to lower pain levels, with bleeding after its use being rare. These findings suggest that ketorolac is well-tolerated in similar surgeries. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for cleft lip and palate focus on surgery and post-operative care involving pain management with opioids. However, Ketorolac is unique because it offers a non-opioid option for pain relief after surgery. This non-steroidal anti-inflammatory drug (NSAID) works by reducing inflammation and pain without the risk of addiction associated with opioids. Researchers are excited about Ketorolac because it could lead to safer pain management for patients, especially children, reducing the reliance on stronger medications.

What evidence suggests that Ketorolac might be an effective treatment for improving oral intake post-operatively in cleft lip and palate patients?

Research shows that ketorolac, which participants in this trial may receive, can aid recovery after surgery. Studies have found that using ketorolac post-surgery reduces the need for stronger painkillers and lowers pain levels. It also helps patients leave the hospital sooner. Specifically, for cleft palate surgery, ketorolac has been linked to better pain control and improved ability to eat and drink, reducing reliance on stronger pain medications. These findings suggest ketorolac effectively improves recovery after oral surgeries. ^{2 5 6 7 8}

Who Is on the Research Team?

Matthew R Grieves, MD,MS,FACS

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for patients with cleft palate, with or without a cleft lip, who haven't had palatoplasty before. It's not for those with kidney issues, bleeding disorders that make NSAIDs risky, GI complications like ulcers or bleeds, syndromic cleft palate conditions, serious heart defects uncorrected by surgery, or if they rely on feeding tubes.

Inclusion Criteria

You have a type of facial difference called cleft palate, which may or may not be accompanied by cleft lip.

Exclusion Criteria

I have a significant untreated heart defect.

I have had surgery to repair my palate.

My parents do not agree to let me be randomly assigned to a treatment group.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IV Ketorolac or placebo as part of multi-modal pain therapy during and immediately after palatoplasty surgery

Immediate post-operative period (up to 24 hours post-surgery)

Follow-up

Participants are monitored for post-operative complications and pain management effectiveness

30 days post-surgery

What Are the Treatments Tested in This Trial?

Interventions

• Ketorolac
• Placebo

Trial Overview The study is testing whether adding IV Ketorolac to the usual pain management after palatoplasty helps improve oral intake post-surgery compared to standard care alone. Participants will either receive Ketorolac or a placebo.

How Is the Trial Designed?

Group I: Experimental group (Ketorolac) Experimental Treatment 1 Intervention

Group II: Control Group Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

In a study of 88 women experiencing preterm labor at less than 32 weeks of gestation, ketorolac was found to be more effective than magnesium sulfate in stopping labor, with an average time of 2.71 hours compared to 6.22 hours for magnesium sulfate.

Both treatments were safe, as no patients had to stop taking either medication due to side effects, and there were no differences in neonatal complications between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of ketorolac (Toradol) and magnesium sulfate for arrest of preterm labor. Schorr, SJ., Ascarelli, MH., Rust, OA., et al.[2019]

In a study of 89 children under 36 months who underwent cleft palate surgery, the use of ketorolac significantly reduced the need for narcotics and improved pain management, as indicated by lower morphine equivalent doses and FLACC scores.

Postoperative bleeding was infrequent in both the ketorolac and non-ketorolac groups, suggesting that ketorolac is a safe option for pain management in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative Use of Ketorolac Improves Pain Management and Decreases Narcotic Use Following Primary Cleft Palate Surgery. Dudley, S., Spence, M., Frederick, R., et al.[2022]

In a study involving 176 postoperative patients, ketorolac (10 mg orally) provided analgesic efficacy comparable to both 5 mg and 10 mg doses of morphine, significantly outperforming placebo.

Ketorolac is a safe and effective option for managing acute postoperative pain, serving as a non-opioid alternative to traditional opioid therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of ketorolac in the management of postoperative pain. DeAndrade, JR., Maslanka, M., Maneatis, T., et al.[2022]

The intranasal formulation of ketorolac tromethamine, known as SPRIX, provides a similar pharmacokinetic profile to intramuscular administration, making it an effective option for treating moderately severe acute pain.

Toxicology studies in rats and rabbits indicate that SPRIX has a safety profile comparable to other administration routes, with no adverse effects observed on the nasal passages or respiratory system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel formulation of ketorolac tromethamine for intranasal administration: preclinical safety evaluation. Boyer, KC., McDonald, P., Zoetis, T.[2013]

In a study involving 40 patients with severe odontogenic pain, ketorolac tromethamine (KT) significantly reduced pain levels compared to a placebo, with patients reporting negligible discomfort by 90 minutes post-injection.

KT effectively alleviates severe pain within 40 minutes of administration, demonstrating its efficacy as an analgesic with minimal side effects, such as lightheadedness and injection site pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization of ketorolac tromethamine for control of severe odontogenic pain. Curtis, P., Gartman, LA., Green, DB.[2013]

In a study involving 30 patients and 60 eyes, the use of ketorolac tromethamine 0.4% (Acular LS) drops significantly reduced postoperative pain after LASIK surgery compared to a placebo (Refresh Tears), with pain scores of 0.53 in the ketorolac group versus 1.23 in the placebo group.

No complications such as flap slips or microstriae were reported, indicating that ketorolac is a safe option for pain management in LASIK procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acular LS before and during LASIK for the control of pain: a randomized, masked contralateral eye trial. Dougherty, PJ.[2021]

A study involving 27 healthy Mexican adults found that two sublingual formulations of 30-mg ketorolac were bioequivalent, meaning they had similar absorption rates and effectiveness in the body.

Both formulations were well tolerated, with only mild adverse events reported, indicating that they are safe for use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability of two sublingual formulations of ketorolac tromethamine 30 mg: a randomized, open-label, single-dose, two-period crossover comparison in healthy Mexican adult volunteers. Galán-Herrera, JF., Poo, JL., Maya-Barrios, JA., et al.[2014]

In a study of 111 patients undergoing primary palatoplasty, a single dose of ketorolac (0.5 mg/kg) was found to be safe, with no significant bleeding complications or need for supplementary oxygen reported post-surgery.

The study did not show a significant difference in pain management or opioid use between the ketorolac group and historical controls, suggesting that while ketorolac is safe, its efficacy in improving pain relief after palatoplasty needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Single-Dose Ketorolac for Postoperative Pain Management After Primary Palatoplasty: A Prospective Cohort Study With Historical Controls. Stein, JR., Mantilla-Rivas, E., Aivaz, M., et al.[2022]

In a study involving 200 patients undergoing photorefractive keratectomy, topical ketorolac tromethamine 0.5% was found to provide significantly greater pain relief compared to its vehicle, with patients experiencing less pain intensity and a longer time before needing additional pain medication.

The ketorolac group also reported fewer side effects, such as sleep difficulties and ocular discomfort, and overall, the treatment was deemed safe with minimal adverse events, indicating its efficacy and safety for post-surgery pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic efficacy and safety of ketorolac after photorefractive keratectomy. Ketorolac Study Group. Rajpal, RK., Cooperman, BB.[2022]

In a retrospective study of breast surgery patients over three years, ketorolac did not significantly increase the risk of postoperative hematoma formation, with rates of 3.5% in those receiving ketorolac compared to 2.5% in those who did not.

The overall hematoma rate for the entire cohort was 2.8%, suggesting that ketorolac can be safely used for postoperative pain control without raising concerns about bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toradol following Breast Surgery: Is There an Increased Risk of Hematoma? Nguyen, BN., Barta, RJ., Stewart, CE., et al.[2021]

Ketorolac tromethamine is a potent nonsteroidal anti-inflammatory drug (NSAID) that provides rapid pain relief, achieving peak effects within one to two hours after intramuscular injection, and has shown effectiveness comparable or superior to opioids like morphine for acute pain management.

While generally safe with mild to moderate side effects, ketorolac can cause gastric ulcerations and has a reversible effect on platelet aggregation, highlighting the need for caution, especially in patients with renal impairment or the elderly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac: a parenteral nonsteroidal antiinflammatory drug. Resman-Targoff, BH.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34514869/

Postoperative Use of Ketorolac Improves Pain ... Use of ketorolac significantly decreased narcotic usage and pain scores as reported by the FLACC score. Moreover, postoperative bleeding was rare.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38794844/

Early Utilization of Ketorolac in Cleft Palate Repair There is a significant relationship between the early utilization of ketorolac and decreased length of hospitalization as well as decreased opiate requirement.

3. journals.sagepub.com journals.sagepub.com/doi/10.1177/10556656241250138

Early Utilization of Ketorolac in Cleft Palate Repair Among patients undergoing palatoplasty, there is a significant relationship between the early utilization of ketorolac and decreased length of ...

4. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/10556656241250138

Early Utilization of Ketorolac in Cleft Palate Repair There is a significant relationship between the early utilization of ketorolac and decreased length of hospitalization as well as decreased opiate requirement.

5. researchgate.net researchgate.net/publication/371950840_The_Limit_Is_Zero_A_Prospective_Evaluation_of_Ketorolac_in_Patients_Undergoing_Primary_Palatoplasty_to_Reduce_Narcotic_Utilization

The Limit Is Zero: A Prospective Evaluation of Ketorolac in ... Our results demonstrated favorable outcomes, including decreased narcotic usage and LOS as well as increased hourly oral intake, without ...

6. withpower.com withpower.com/trial/phase-4-cleft-lip-2-2021-688e4

Ketorolac for Cleft Lip and Palate In a study of 111 patients undergoing primary palatoplasty, a single dose of ketorolac (0.5 mg/kg) was found to be safe, with no significant bleeding ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33942669/

Safety and Efficacy of Single-Dose Ketorolac for ... This is the first prospective study to evaluate the safety and efficacy of single-dose ketorolac after PP.

8. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/10556656211012864

Safety and Efficacy of Single-Dose Ketorolac for ... This is the first prospective study to evaluate the safety and efficacy of single-dose ketorolac after PP.