Azithromycin for Maternal Obesity

Overseen By Christy Zornes, MHR

Age: < 65

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Oklahoma

Must not be taking: Azithromycin, Beta-lactam antibiotics

Disqualifiers: Fetal anomaly, Multiple gestation, others

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: Unknown

Duration: During labor induction

787 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether administering the antibiotic azithromycin during labor can reduce the likelihood of cesarean delivery in pregnant women classified as obese. Obese women often face higher risks during pregnancy, including an increased chance of needing a C-section. Researchers aim to make labor safer and reduce these risks by using azithromycin. The trial seeks pregnant women with a BMI of 30 or more who have reached at least 37 weeks of pregnancy and are undergoing labor induction for the first time. As a Phase 2 trial, this research measures how well azithromycin works in an initial, smaller group, offering participants a chance to contribute to potentially safer labor practices.

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?

A study with nearly 4,000 patients found azithromycin to be safe, with only about 12% experiencing side effects. Another study demonstrated that giving azithromycin to pregnant women improved health outcomes for both mothers and babies, indicating it is generally well-tolerated. Its use for other conditions further supports its safety. However, since this trial is in an early phase, the focus remains on understanding the treatment's safety and effectiveness, with more information to be gathered as research continues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using azithromycin for maternal obesity because it takes a unique approach by incorporating antibiotics to potentially reduce inflammation and improve metabolic outcomes. Unlike typical treatments for obesity, which often focus on lifestyle changes or hormone regulation, azithromycin targets underlying inflammatory processes that might contribute to obesity-related complications during pregnancy. This approach could offer a novel way to address the condition, providing benefits beyond traditional methods.

What evidence suggests that this trial's treatments could be effective for reducing cesarean delivery rates in obese women?

This trial will compare the effects of azithromycin with a placebo in pregnant women with obesity. Studies have shown that azithromycin can benefit pregnant women and their babies. Specifically, past research demonstrated that using azithromycin during labor improved outcomes for mothers and newborns. For women with obesity, azithromycin reduced the need for a cesarean section and lowered the risk of post-surgery infections. Additionally, azithromycin is generally safe, with only a few experiencing side effects. These findings suggest that azithromycin could help reduce complications during labor for women with obesity. ^{1 3 4 6 7}

Who Is on the Research Team?

Stephanie Pierce, MD

Principal Investigator

University of Oklahoma

Are You a Good Fit for This Trial?

This trial is for obese women who are pregnant for the first time (nulliparous) and are at term, meaning they're close to their due date. They must be planning to induce labor and have not given birth before. The study is specifically looking at those with a high body mass index (BMI).

Inclusion Criteria

No prior deliveries at or beyond 20 weeks gestation

Undergoing induction of labor

My pregnancy has reached 37 weeks or more.

Exclusion Criteria

Fetal death prior to labor induction

Known fetal anomaly

Multiple gestation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either prophylactic antibiotics or placebo during labor induction

During labor induction

In-person visits during labor

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days postpartum

Follow-up visits as needed

What Are the Treatments Tested in This Trial?

Interventions

• Azithromycin

Trial Overview The trial is testing whether giving an antibiotic called Azithromycin before inducing labor can lower the rate of cesarean deliveries in obese women having their first child. Some participants will receive this antibiotic, while others will get a placebo, which has no active ingredients.

How Is the Trial Designed?

Group I: Prophylactic antibiotics Active Control 1 Intervention

Azithromycin 500 milligrams intravenously once and cefazolin 2 grams intravenously every 8 hours for up to three doses

Group II: Placebo Placebo Group 1 Intervention

Placebos, similar in appearance, in place of azithromycin and cefazolin

Azithromycin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Azithromycin for:

• Respiratory tract infections
• Skin and soft tissue infections
• Sexually transmitted diseases
• Toxoplasmosis
• Malaria
• Preterm prelabor rupture of membranes

Approved in United States as Azithromycin for:

• Respiratory tract infections
• Skin and soft tissue infections
• Sexually transmitted diseases
• Toxoplasmosis
• Malaria
• Preterm prelabor rupture of membranes

Approved in Canada as Azithromycin for:

• Respiratory tract infections
• Skin and soft tissue infections
• Sexually transmitted diseases
• Toxoplasmosis
• Malaria
• Preterm prelabor rupture of membranes

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

University of Florida

Collaborator

Trials

1,428

Recruited

987,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Case Western Reserve University

Collaborator

Trials

314

Recruited

236,000+

Published Research Related to This Trial

A pilot study involving 41 pregnant women with overweight or obesity found that a lifestyle modification program delivered via phone did not significantly reduce gestational weight gain compared to standard treatment.

Both the intervention and standard treatment groups had similar outcomes in terms of weight gain during pregnancy and postpartum, suggesting that more intensive or earlier interventions may be needed to effectively manage weight during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Randomized Controlled Trial of a Technology-Based Approach for Preventing Excess Weight Gain during Pregnancy among Women with Overweight. Chao, AM., Srinivas, SK., Studt, SK., et al.[2023]

A scoping review of 90 studies, including 87 randomized controlled trials, found that behavioral interventions focusing on diet and physical activity are effective in helping women of childbearing age prevent excessive weight gain during pregnancy and retain a healthy weight postpartum.

Despite the growing research on weight management for pregnant and postpartum women, there is a notable lack of studies addressing weight management for young adult women outside of pregnancy or preconception contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supporting women of childbearing age in the prevention and treatment of overweight and obesity: a scoping review of randomized control trials of behavioral interventions. Hutchesson, MJ., de Jonge Mulock Houwer, M., Brown, HM., et al.[2023]

Maternal obesity significantly increases the risk of pregnancy complications, including gestational diabetes, preeclampsia, and delivery issues such as macrosomia and higher cesarean section rates.

Obesity during pregnancy is also linked to serious outcomes for the fetus, including an increased risk of neural tube defects and fetal mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal obesity and complications during pregnancy. Dietl, J.[2007]

Pregnant women with obesity, especially those classified as class III and super morbid obesity, face unique medical challenges and increased risks for both themselves and their fetuses during all stages of pregnancy.

The document emphasizes the need for careful consideration and tailored care strategies to address the specific health risks associated with obesity in pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnancy Care for Patients With Super Morbid Obesity. Olerich, K., Soper, D., Delaney, S., et al.[2022]

In a study of 3,995 patients aged 2-94, azithromycin demonstrated a favorable safety profile, with only 12.0% of patients experiencing side effects, which is significantly lower than the 14.2% seen with other standard antibiotics.

The most common side effects were mild to moderate gastrointestinal issues, and only 0.7% of patients discontinued treatment due to side effects, indicating that azithromycin is well tolerated even among patients with various concurrent illnesses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical toleration and safety of azithromycin. Hopkins, S.[2022]

A meta-analysis of nine studies involving 3,597 pediatric patients found that azithromycin has a statistically significant lower risk of adverse events compared to other antibiotics, indicating its relative safety in treating infectious diseases in children.

While azithromycin is generally safe, caution is advised with higher dosages, suggesting that careful monitoring is necessary to avoid potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of azithromycin in pediatric infectious diseases: a clinical systematic review and meta-analysis. Li, D., Wang, Y.[2022]

Azithromycin significantly reduces the risk of bronchopulmonary dysplasia (BPD) in extremely premature neonates, with a relative risk of 0.83 based on a review of 11 studies involving 473 neonates.

While azithromycin is associated with various adverse events, including respiratory and gastrointestinal issues, there was no significant increase in liver enzyme levels compared to placebo, indicating a relatively safe profile for this medication in neonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use and safety of azithromycin in neonates: a systematic review. Smith, C., Egunsola, O., Choonara, I., et al.[2022]

The implementation of a clinical carepath for obese pregnant women improved adherence to guideline recommendations compared to standard care, with a relative risk of 1.71, indicating a significant benefit in care quality.

While the carepath was feasible for many screening recommendations, its uptake among eligible women was less than 80%, suggesting challenges in full implementation across mixed obstetric and midwifery clinics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical carepath for obese pregnant women: a pragmatic pilot cluster randomized controlled trial. McDonald, SD., Viaje, KA., Rooney, RA., et al.[2020]

The study analyzed azithromycin pharmacokinetics in 53 pregnant and 25 nonpregnant women, revealing that pregnancy and factors like lean body weight and ethnicity significantly affect how the drug is processed in the body.

Pregnant women who are not African American may experience 21% to 42% higher drug exposure compared to nonpregnant women, suggesting that dose adjustments may be necessary to avoid excessive exposure during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of body weight, ethnicity, oral contraceptives, and pregnancy on the pharmacokinetics of azithromycin in women of childbearing age. Fischer, JH., Sarto, GE., Habibi, M., et al.[2021]

Azithromycin is generally considered a safe medication, with serious side effects like angioedema and cholestatic jaundice occurring in less than 1% of patients.

However, this report highlights a rare but severe case of dilated cardiomyopathy and significant liver toxicity leading to hepatic encephalopathy in a patient taking Azithromycin, suggesting that even commonly used medications can have unexpected serious effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin induced hepatocellular toxicity and hepatic encephalopathy in asymptomatic dilated cardiomyopathy. Das, BK.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11253273/

PeRinatal, neOnatal, and Maternal OuTcomEs with ... Initial randomised controlled trials (RCTs) showed that prophylactic azithromycin in pregnant women improved maternal and neonatal outcomes; ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1876034120305542

Strong association between adolescent obesity and ... We found that in both the USA and Europe, population level consumption of macrolides was positively associated with subsequent childhood obesity prevalence.

3. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/adjunctive-azithromycin-in-obese-patients-undergoing-unscheduled-c-sections

Adjunctive Azithromycin in Obese Patients Undergoing ... The study also showed that standard-dose azithromycin reduces readmission/unscheduled visits in patients with class III obesity.

4. withpower.com withpower.com/trial/phase-2-obstetric-labor-complications-7-2024-480dd

Azithromycin for Maternal Obesity In a study of 3,995 patients aged 2-94, azithromycin demonstrated a favorable safety profile, with only 12.0% of patients experiencing side effects, which is ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37487546/

Standard-Dose Azithromycin in Class III Obese Patients ... Conclusion: A standard dose of azithromycin provides adequate perioperative prophylaxis in class III obese patients, decreasing rates of postcesarean wound ...

6. ajog.org ajog.org/article/S0002-9378(21)02039-1/fulltext

Antibiotic Prophylaxis to Prevent Obesity-Related Induction ... Conclusion. Administration of prophylactic antibiotics during labor induction in obese nulliparous patients resulted in numerically lower cesarean delivery and ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0024320523006203

Azithromycin exposure during pregnancy disturbs the fetal ... Initial randomised controlled trials (RCTs) showed that prophylactic azithromycin in pregnant women improved maternal and neonatal outcomes; ...