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

Trial Summary

What is the purpose of this trial?

Obesity increases the risk of pregnancy complications, including puerperal infections and cesarean delivery, and risk rises with increasing body mass index (BMI). Since obese women are more likely to have comorbidities that would necessitate delivery prior to their due date (i.e. prior to 40 weeks gestation), and class III obesity specifically is an indication for delivery by 39 weeks, these patients have a high rate of labor induction. In nulliparous women from the general population (obese and non-obese), labor induction at 39 weeks (compared to expectant management) is associated with less maternal morbidity and a lower cesarean rate. Researchers previously conducted a pilot randomized placebo-controlled trial in obese, nulliparous women undergoing labor induction at term and found that the cesarean delivery rate was lower in women who received a prophylactic antibiotic regimen during labor compared with those who received the placebo. Researchers proposed multi-center trial aims to test this hypothesis in a large sample with adequate power to determine whether prophylactic antibiotics during labor are associated with a decrease in the rate of cesarean delivery in term, nulliparous, obese women. If the findings from the pilot trial are confirmed, this would represent a novel intervention to decrease the cesarean delivery rate in a subset of women at highest risk for cesarean-related complications.

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 azithromycin generally safe for humans?

Azithromycin is generally considered safe for humans, with common side effects like diarrhea and abdominal pain being mild or moderate. Serious side effects are rare, occurring in less than 1% of patients, but can include liver issues and allergic reactions. It is well tolerated in a variety of conditions and with other medications. ^{1 2 3 4 5}

How does the drug Azithromycin differ from other treatments for maternal obesity?

Azithromycin is an antibiotic typically used to treat infections, and its use for maternal obesity is unique because it is not a standard treatment for this condition. Unlike lifestyle or behavioral interventions commonly used to manage weight during pregnancy, Azithromycin's role in this context may involve addressing infection-related complications associated with obesity. ^{6 7 8 9 10}

Research Team

Stephanie Pierce, MD

Principal Investigator

University of Oklahoma

Eligibility Criteria

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

My pregnancy has reached 37 weeks or more.

No prior deliveries at or beyond 20 weeks gestation

I am between 15 and 45 years old.

Exclusion Criteria

Fetal death prior to labor induction

Known fetal anomaly

Multiple gestation

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

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

Clinical toleration and safety of azithromycin. [2022]

2. China pubmed.ncbi.nlm.nih.gov

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

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

Influence of body weight, ethnicity, oral contraceptives, and pregnancy on the pharmacokinetics of azithromycin in women of childbearing age. [2021]

4. India pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Use and safety of azithromycin in neonates: a systematic review. [2022]

6. Switzerland 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

A clinical carepath for obese pregnant women: a pragmatic pilot cluster randomized controlled trial. [2020]

8. England 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. [2023]

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

Maternal obesity and complications during pregnancy. [2007]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Pregnancy Care for Patients With Super Morbid Obesity. [2022]