Buprenorphine Patch for Opioid Addiction in Pregnancy

(Patch BRIDGE Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Jeannie C Kelly, MD, MS

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Washington University School of Medicine

Disqualifiers: Current treatment, Prior induction, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to compare buprenorphine patch for induction (starting) of buprenorphine in pregnant patients with opioid use disorder. The main questions it aims to answer are: 1. Is there a buprenorphine induction method that results in the least moderate-to-severe opioid withdrawal symptoms in pregnant patients with opioid use disorder? 2. Is there a buprenorphine induction method that results in a higher treatment success rate? Under normal circumstances, patients who are planning to start sublingual (under the tongue) buprenorphine for opioid use disorder must first go into withdrawal to start the medication safely. Study participants will be given a buprenorphine patch during the required withdrawal period before starting sublingual treatment, and be surveyed daily by phone to assess their withdrawal symptoms. They will also be followed at prenatal appointments to evaluate treatment success based on urine drug screen results. Researchers will compare patients receiving no buprenorphine patch according to the current standard care protocol.

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

The trial does not specify if you need to stop taking your current medications, but it does require that you are not already receiving treatment for opioid use disorder.

What data supports the effectiveness of the drug Buprenorphine Transdermal Matrix Patch for opioid addiction in pregnancy?

Buprenorphine patches have been shown to be effective in managing chronic pain, providing consistent pain relief and being well-tolerated over long periods. While these studies focus on pain management, the drug's ability to deliver consistent doses and its safety profile suggest potential benefits for managing opioid addiction in pregnancy.

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Is the Buprenorphine Patch safe for use in humans, including during pregnancy?

There is no specific safety data available for the Buprenorphine Patch in pregnancy from the provided research articles. However, pregnancy registries are often used to monitor drug safety during pregnancy, suggesting that such data might exist elsewhere for Buprenorphine or similar medications.

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How is the buprenorphine patch unique for treating opioid addiction in pregnancy?

The buprenorphine patch is unique because it provides a continuous, steady release of medication through the skin, which can help maintain stable drug levels and reduce withdrawal symptoms without the need for frequent dosing. This transdermal (through the skin) delivery system is convenient and may be better tolerated than other forms of buprenorphine, making it a potentially safer option during pregnancy.

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Eligibility Criteria

This trial is for pregnant individuals who have opioid use disorder and want to start buprenorphine treatment. They must have used opioids within the last 24 hours, be receiving prenatal care at a specific clinic, and not have tried buprenorphine induction before or need immediate hospitalization.

Inclusion Criteria

Opioid use within 24 hours prior to presentation

I want to be treated with buprenorphine.

Viable pregnancy

Exclusion Criteria

I cannot take buprenorphine due to health reasons.

Patients already receiving treatment for opioid use disorder

I need to be hospitalized right away.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive a buprenorphine patch during the required withdrawal period before starting sublingual treatment. They are surveyed daily by phone to assess withdrawal symptoms.

1 week

Daily phone surveys

Treatment

Participants are followed at prenatal appointments to evaluate treatment success based on urine drug screen results.

From induction to delivery

Regular prenatal appointments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The study tests if a buprenorphine patch can help manage withdrawal symptoms better than no patch during the period before starting sublingual buprenorphine. Success of the treatment will be monitored through daily phone surveys and urine drug screens at prenatal visits.

Group I: Bridge Induction Arm Experimental Treatment 1 Intervention

Group II: Standard Arm Placebo Group 1 Intervention

Buprenorphine Transdermal Matrix Patch is already approved in United States, European Union, Canada, Australia for the following indications:

🇺🇸 Approved in United States as Butrans for:

• Severe pain
• Chronic pain
• Opioid use disorder

🇪🇺 Approved in European Union as BuTrans for:

• Severe pain
• Chronic pain
• Opioid dependence

🇨🇦 Approved in Canada as Transtec for:

• Severe pain
• Chronic pain

🇦🇺 Approved in Australia as Norspan for:

• Severe pain
• Chronic pain

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Washington University in St. Louis Saint Louis, MO

Who Is Running the Clinical Trial?

Washington University School of Medicine Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Transdermal buprenorphine for the treatment of moderate to severe chronic pain: results from a large multicenter, non-interventional post-marketing study in Poland. [2013] To evaluate the use of a buprenorphine transdermal patch (Transtec*) in routine clinical practice, including dosage, indications, efficacy and tolerability.

2. England pubmed.ncbi.nlm.nih.gov

Transdermal buprenorphine in the treatment of chronic pain. [2022] The transdermal matrix patch formulation of buprenorphine has been shown to be effective in managing moderate-to-severe cancer pain and severe pain unresponsive to nonopioid analgesics. Clinical trials have revealed that it is possible to switch from weak opioids or low doses of step III opioids to transdermal buprenorphine without any problems. With buprenorphine patches, the sublingual buprenorphine intake was dose-dependently reduced and was superior to placebo in this respect. The proportion of responders increased with the buprenorphine dose, and a higher proportion of patients receiving buprenorphine patches reported uninterrupted sleep for longer than 6 h compared with those receiving placebo. In a long-term, open, follow-up study in which the mean duration of treatment was 7.5 months, analgesia was rated as at least satisfactory by 90% of patients. Almost 60% of patients could manage their pain with one patch alone or with one additional sublingual tablet a day during the whole period of treatment, indicating a low incidence of tolerance development. The buprenorphine transdermal patch was assessed as user friendly by 94.6% of patients. In a postmarketing surveillance study, pain relief with transdermal buprenorphine was rated as good or very good by 70% of the responders. Postmarketing surveillance studies have shown that transdermal buprenorphine is also effective in the management of nociceptive and neuropathic pain, which some studies have shown to be relatively insensitive to mu-opioid analgesics, such as morphine. Transdermal buprenorphine was well tolerated. Most adverse events were either local reactions to the patch that generally subsided within 24 h or systemic events typical of treatment with opioid analgesics, such as nausea, vomiting and constipation.

3. Germany pubmed.ncbi.nlm.nih.gov

[Transdermal buprenorphine during pregnancy]. [2018] Buprenorphine has been widely used and studied for over 20 years and has been shown to be an effective opioid analgesic. Some years ago a buprenorphine formulation for transdermal therapy of chronic cancer-related and non-cancer-related pain became available. We report the case of a woman who received a lower dosed transdermal buprenorphine patch (3/5 of a 35 microg/h patch corresponding to release of 21 microg/h buprenorphine) during pregnancy without any complication for herself or the child. The patient has now being using the transdermal system for more than 2 years and has reported continuous excellent pain relief. The buprenorphine patch was well tolerated and produced no effect on vigilance over the whole period of administration.

4. New Zealand pubmed.ncbi.nlm.nih.gov

Buprenorphine 5, 10 and 20 μg/h transdermal patch: a review of its use in the management of chronic non-malignant pain. [2022] This article reviews the pharmacology, therapeutic efficacy and tolerability profile of the 7-day lower-dose (5, 10 and 20 μg/h) buprenorphine transdermal patch (BuTrans®, Norspan®) in the management of chronic non-malignant pain, with a focus on European labelling for the drug. Buprenorphine is a semi-synthetic opioid analgesic that acts primarily as a partial agonist at the mu opioid receptor. The transdermal formulation provides continuous delivery of buprenorphine, resulting in relatively consistent plasma drug concentrations throughout the 7-day dosing interval. The analgesic efficacy of transdermal buprenorphine in patients with osteoarthritis of the hip and/or knee has been demonstrated in several randomized controlled trials, which have shown the formulation to be equivalent to sublingual buprenorphine, noninferior to prolonged-release tramadol tablets, noninferior to codeine plus paracetamol (acetaminophen) combination tablets (when transdermal buprenorphine was used together with regularly scheduled oral paracetamol) and generally superior to a matching transdermal placebo patch. Transdermal buprenorphine was significantly more effective than placebo in reducing chronic low back pain of at least moderate severity in two randomized, double-blind, crossover trials. Other clinical trials, including a randomized, double-blind, maintenance-of-analgesia study, have also demonstrated the analgesic efficacy of transdermal buprenorphine in patients with chronic non-malignant pain of various causes. In general, serious adverse events with transdermal buprenorphine are similar to those for other opioid analgesics. Transdermal buprenorphine has a ceiling effect for respiratory depression, and the main risk is when it is combined with other CNS depressants. The most frequently reported adverse events with transdermal buprenorphine are headache, dizziness, somnolence, constipation, dry mouth, nausea, vomiting, pruritus, erythema, application site pruritus and application site reactions. Transdermal buprenorphine was better tolerated than sublingual buprenorphine in a 7-week, randomized, double-blind trial in patients with osteoarthritis pain. Nevertheless, as with other opioids, persistence with transdermal buprenorphine therapy is difficult for many patients because of adverse events or other reasons. Thus, transdermal buprenorphine has generally demonstrated good efficacy and tolerability in clinical trials in chronic non-malignant pain, providing effective background analgesia as part of pain management strategies for patients with osteoarthritis, low back pain and other persistent pain syndromes of at least moderate severity. It also has favourable pharmacodynamic and pharmacokinetic properties, which have beneficial clinical implications, most notably the convenience of once-weekly administration and no need for dosage adjustments in the elderly or those with compromised renal function, making it an opioid of choice in these patients, and a useful therapeutic option overall in the management of chronic non-malignant pain.

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

Transdermal buprenorphine patches applied in a 4-day regimen versus a 3-day regimen: a single-site, Phase III, randomized, open-label, crossover comparison. [2013] In 2001, a transdermal matrix patch formulation of buprenorphine was approved for the treatment of moderate to severe cancer pain and severe pain that is unresponsive to nonopioid analgesics. The primary recommendation contained in the prescribing information was that transdermal patches be worn for a 3-day period before application of a new patch.

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Non-compliance with pregnancy prevention recommendations for isotretinoin in Korea between 2019-2020. [2021] Isotretinoin is commonly prescribed worldwide despite its notorious teratogenicity. A risk management program (RMP) was introduced in Korea to prevent isotretinoin use during pregnancy. Here, we evaluate the compliance of Korean women with the recommendations of the RMP.

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

The Pregnancy Registry program at Glaxo Wellcome Company. [2019] Registries can be used to provide an early warning system for potential teratogenic effects associated with the use of specific medications during pregnancy. Glaxo Wellcome has developed 5 international registries: (1) the Acyclovir Pregnancy Registry, (2) the Antiretroviral Pregnancy Registry, (3) the Lamotrigine Pregnancy Registry, (4) the Sumatriptan Pregnancy Registry, and (5) the Bupropion Pregnancy Registry. The purpose of these registries is to gain more information about the potential teratogenicity of these drugs during pregnancy. Two potential limitations of such registry data are recognized: (1) the utility of the data collected depends on the size of the sample; and (2) the registered patients may not be representative of all patients using the medication. However, these types of registry reports can be a valuable and cost-effective way to collect data regarding the use of medications during pregnancy when conventional methods (eg, cohort studies) are not appropriate or feasible.

8. New Zealand pubmed.ncbi.nlm.nih.gov

Can we ensure the safe use of known human teratogens? Introduction of generic isotretinoin in the US as an example. [2018] The prescription of known teratogenic medications requires a careful balance between allowing women access to medications that they might need and avoiding unnecessary exposure to these medications during pregnancy because of their devastating fetal effects. Isotretinoin, a potent human teratogen, is of particular concern because of its widespread use among reproductive-aged women and the dramatic increase in use from 1992 through 2000. A revised risk management system was implemented in 2002 because of concerns about the continued occurrence of isotretinoin-exposed pregnancies. However, the recent approval of three generic versions of isotretinoin in the US has further complicated risk management and raises concerns that use might increase further if the lower cost of generics serves to increase accessibility. There are now four separate isotretinoin risk management systems in the US, each with its own distinct packaging, though the requirements for and substance of each are identical. Some additional concrete steps could be taken to minimise any unnecessary use of isotretinoin and help allow an adequate assessment of the current risk management systems. In addition to being familiar with and following all aspects of the current risk management system, physicians could choose to limit the use of isotretinoin to those who meet the labelled indications in order to reduce the number of exposed pregnancies. All four companies currently marketing isotretinoin in the US could jointly and voluntarily establish a consolidated, mandatory registration and follow-up of all women of reproductive potential who receive an isotretinoin prescription. Mandatory registration has many challenges, but it could allow a clear accounting of the total number of women for whom follow-up information is and is not available. Although the companies cannot be legally compelled to use a consolidated approach, the use of a single registry for the originator's product and all generic brands would allow identification of duplicates and also avoid the confusion that is introduced by providing materials that not only look different, but also have different addresses, contact information and names for participation in follow-up surveys. This is particularly important because women might take more than one version of isotretinoin during a single course of therapy or might receive a different programme's materials from their doctor than from the pharmacy. Though the introduction of generic versions of isotretinoin further complicates risk management, the companies marketing isotretinoin have an opportunity to work together to demonstrate their commitment to both limit the occurrence of exposed pregnancies and conduct a meaningful evaluation of the occurrence of pregnancies exposed to isotretinoin.

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

The antiretrovirals in pregnancy registry: a fifteenth anniversary celebration. [2013] The year 2007 marks the fifteenth anniversary year of the founding of a landmark effort in drug safety risk management, the formation of the first monitoring effort of an antiretroviral (ARV) drug in pregnancy which has become the Antiretrovirals in Pregnancy Registry, the APR. This multicompany, multi-national voluntary collaborative registry monitors pregnancy exposure to a class of highly important drugs for any indication of an increase in the postexposure incidence of birth defects in the offspring of these pregnancies. To recognize the anniversary, the Steering Committee of the APR has commissioned this review of the contributions and lessons learned over the past decade and a half and, in the spirit of continuous process improvement, has committed to apply these lessons for the next fifteen years. This retrospective examines the antecedents to this registry and the context in which the APR was formed; the early efforts to establish technical and organizational procedures and policies; the evolving experiences with enrollment and follow-up, patient and participant protections, information management and oversight; public and regulatory dissemination; and of course, the accomplishments and lessons learned.

10. New Zealand pubmed.ncbi.nlm.nih.gov

Monitoring outcomes of pregnancy following drug exposure: a company-based pregnancy registry program. [2018] Women who discover they are pregnant after exposure to a drug and pregnant women who have a condition that requires continued treatment during pregnancy are told to balance the benefits and risks of the exposure to justify continuation of treatment, discontinuation of treatment or, possibly, pregnancy termination. However, there are limited data available to inform decision-making. The Merck Pregnancy Registry Program is a company-run pregnancy registry whose objective is to acquire and analyse information on drug exposures and pregnancy outcomes to better describe the safety profile of Merck products used during pregnancy. Information is collected from women and healthcare providers who call to report drug exposure during pregnancy. Prospective pregnancies are followed up to outcome and data are collected via questionnaires, telephone calls and a review of medical records. Reports are classified as prospective (information received prior to knowledge of pregnancy outcome) or retrospective (received after the outcome is known). Congenital anomaly reports are assessed for timing of exposure, maternal age and medical history, biological plausibility and concomitant medication exposures. Rates of pregnancy outcomes and birth defects in the prospective cohort are computed and confidence intervals are calculated to reflect the strength of the finding based on the sample size. Rates of pregnancy outcomes in the Pregnancy Registry are compared with the rates of pregnancy outcomes in the general US population and, if available, in subpopulations with the relevant disease states. The limitations of post-marketing surveillance are well known as voluntary reporting of individuals and healthcare professionals is known to be subject to various types of bias. Small sample size is another major limitation. However, the strength of the registry lies in its ability to gather pregnancy outcome reports early in the life of a product and to recognise and analyse unusual birth defects. Our data suggest that pregnancy registries can be used to review human exposure data in a systematic fashion so that useful information can be shared with women and their healthcare providers. The use of the pregnancy registry design has allowed for the collection and analysis of data on the effects of drug exposures on human pregnancies that have otherwise been difficult to obtain.