Azithromycin for Reducing Infections During Labor

Overseen By Kristina Roloff, DO

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Arrowhead Regional Medical Center

Must not be taking: Antibiotics, Antivirals

Disqualifiers: Active infection, Substance abuse, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

400 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used antibiotics or antiviral agents in the last 7 days before joining.

What data supports the effectiveness of the drug Azithromycin for reducing infections during labor?

Research shows that a single oral dose of azithromycin given to women in labor can reduce certain maternal and neonatal infections, as demonstrated in a trial in The Gambia. Additionally, a large clinical trial found that adding azithromycin to standard antibiotics during cesarean delivery decreased postoperative infections by about 50%. ^{1 2 3 4 5}

Is azithromycin safe for use in humans?

Azithromycin is generally safe for humans, with side effects like diarrhea and abdominal pain occurring in about 12% of patients, mostly mild or moderate. Serious side effects are rare, and it is well tolerated even with other illnesses and medications. ^{1 6 7 8 9}

How is the drug azithromycin unique in reducing infections during labor?

Azithromycin is unique because it is given as a single oral dose during labor and has a broad spectrum of activity, particularly effective against certain bacteria like Haemophilus influenzae. It achieves higher tissue concentrations and is selectively delivered to infected tissues, which may help reduce maternal and neonatal infections more effectively than other antibiotics. ^{1 3 10 11 12}

What is the purpose of this trial?

This is a double blinded randomized control trial involving administration of 2 grams prophylactic azithromycin in third trimester patients undergoing induction of labor at our institution to demonstrate reduction in maternal and neonatal infection.

Eligibility Criteria

This trial is for pregnant women in their third trimester (28 weeks or more) who are undergoing labor induction. Participants should be aged 18-45, have a single pregnancy with no complications that would prevent vaginal delivery, and can give informed consent. Women with recent antibiotic use, active infections, substance abuse issues, or inability to understand English or Spanish are excluded.

Inclusion Criteria

Reassuring fetal heart rate tracing

My labor was started by a doctor for health reasons or by choice after 39 weeks.

I am in my third trimester of pregnancy, beyond 28 weeks.

Exclusion Criteria

Does not read or write in English or Spanish

Active substance abuse

I am currently incarcerated.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Administration of 2 grams oral azithromycin or placebo prior to the start of induction of labor

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on reduction in maternal and neonatal infections

6 weeks postpartum

Treatment Details

Interventions

• Azithromycin

Trial Overview The study tests if taking a one-time dose of 2 grams of Azithromycin before inducing labor can reduce maternal and neonatal infections. It's a double-blind trial meaning neither the participants nor the researchers know who gets the real medicine versus a placebo.

Participant Groups

Group I: Azithromycin Arm Active Control 1 Intervention

Administration of 2 grams oral azithromycin (4 tablets of 500 mg) prior to the start of induction , once.

Group II: Placebo Arm Placebo Group 1 Intervention

Administration of 4 magnesium oxide tablets prior to the start of induction , once.

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?

Arrowhead Regional Medical Center

Lead Sponsor

Trials

18

Recruited

28,200+

Findings from Research

A large, multinational randomized trial is underway to evaluate whether a single oral dose of 2 g azithromycin given to women in labor can reduce maternal and neonatal sepsis and mortality, involving 34,000 participants across multiple regions.

This study aims to provide critical data on the efficacy of azithromycin in preventing infections during labor, which could significantly impact maternal and neonatal health outcomes in areas with high rates of infection-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of maternal and neonatal death/infections with a single oral dose of azithromycin in women in labour in low-income and middle-income countries (A-PLUS): a study protocol for a multinational, randomised placebo-controlled clinical trial. Hemingway-Foday, J., Tita, A., Chomba, E., et al.[2023]

In a study involving 756 laboring women, a single dose of oral azithromycin, with or without amoxicillin, did not significantly reduce the rates of maternal peripartum or neonatal infections compared to a placebo.

However, the combination of azithromycin and amoxicillin did show a significant reduction in chorioamnionitis and wound infections compared to the placebo group, suggesting some targeted benefits despite the overall lack of effect on broader infection rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Dose of Oral Azithromycin With or Without Amoxicillin to Prevent Peripartum Infection in Laboring, High-Risk Women in Cameroon: A Randomized Controlled Trial. Subramaniam, A., Ye, Y., Mbah, R., et al.[2023]

In a study involving 29,278 women planning vaginal delivery, a single 2-g oral dose of azithromycin significantly reduced the risk of maternal sepsis or death compared to placebo (1.6% vs. 2.4%), indicating its efficacy in preventing maternal infections during labor.

However, azithromycin did not significantly impact the rates of stillbirth, neonatal death, or neonatal sepsis, suggesting that while it is beneficial for maternal health, it does not improve outcomes for newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth. Tita, ATN., Carlo, WA., McClure, EM., et al.[2023]

In a study of 2,339 women undergoing cesarean delivery, adding azithromycin to standard preoperative antibiotics did not significantly reduce the overall rate of postoperative infections compared to standard prophylaxis alone.

The results suggest that while azithromycin may have benefits for certain groups (like women in labor), its effectiveness may be limited, especially for women not in labor, indicating that the practice change may not yield the expected benefits in all cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of adding azithromycin to antimicrobial prophylaxis for cesarean delivery. Pierce, SL., Bisson, CM., Dubois, ME., et al.[2022]

In a study of 254 women (127 receiving azithromycin and 127 controls), the addition of azithromycin to standard treatments for preterm labor did not significantly prolong pregnancy or improve gestational age outcomes.

Despite being used in a higher-risk population, the use of azithromycin showed no clear benefits compared to standard care, indicating that its efficacy in this context is questionable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Azithromycin on Pregnancy Prolongation in Women at Risk of Preterm Labor: A Time-to-Event Analysis. Goyer, I., Ferland, G., Ruo, N., et al.[2020]

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]

Azithromycin is an effective broad-spectrum antibiotic with a long half-life and good tissue penetration, making it suitable for treating various infections, including respiratory and sexually transmitted infections.

While azithromycin has beneficial immunomodulatory effects for chronic respiratory diseases, it carries risks of serious side effects like cardiovascular arrhythmias and hearing loss, and there are concerns about macrolide resistance and drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribing azithromycin. McMullan, BJ., Mostaghim, M.[2023]

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 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 is highly effective against a range of bacteria, including Staphylococcus aureus and Haemophilus influenzae, showing particularly strong activity against H. influenzae compared to other macrolides.

After oral administration, azithromycin is well-absorbed and distributed throughout the body, achieving higher concentrations in infected tissues due to its selective delivery by phagocytes, leading to successful treatment outcomes for respiratory infections with a convenient 3-day dosing regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological and pharmacokinetic properties of azithromycin (Zithromac), a novel 15-membered ring macrolide antibacterial agent]. Matsunaga, T.[2019]

Azithromycin is an effective antimicrobial agent against common lower respiratory tract pathogens, showing superior activity against Haemophilus influenzae compared to other macrolides.

Clinical studies demonstrate that a short course of azithromycin (3 or 5 days) is as effective as a longer 10-day course of traditional antibiotics, which may improve patient compliance and reduce treatment duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin in lower respiratory tract infections. Lode, H., Schaberg, T.[2013]

In a study of 60 pregnant women with preterm labor or PROM, a single dose of azithromycin did not significantly reduce colonization of Ureaplasma urealyticum compared to a placebo, with colonization rates remaining high in both groups.

Although azithromycin treatment showed a lower rate of vertical transmission of U. urealyticum (20% vs. 50% in controls), the overall ineffectiveness in reducing colonization suggests that azithromycin may not be a reliable treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of azithromycin in reducing lower genital Ureaplasma urealyticum colonization in women at risk for preterm delivery. Ogasawara, KK., Goodwin, TM.[2008]

References

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

Prevention of maternal and neonatal death/infections with a single oral dose of azithromycin in women in labour in low-income and middle-income countries (A-PLUS): a study protocol for a multinational, randomised placebo-controlled clinical trial. [2023]

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

Single Dose of Oral Azithromycin With or Without Amoxicillin to Prevent Peripartum Infection in Laboring, High-Risk Women in Cameroon: A Randomized Controlled Trial. [2023]

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

Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth. [2023]

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

Clinical effectiveness of adding azithromycin to antimicrobial prophylaxis for cesarean delivery. [2022]

5. Australia pubmed.ncbi.nlm.nih.gov

Impact of Azithromycin on Pregnancy Prolongation in Women at Risk of Preterm Labor: A Time-to-Event Analysis. [2020]

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

Clinical toleration and safety of azithromycin. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Prescribing azithromycin. [2023]

8. England pubmed.ncbi.nlm.nih.gov

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

9. China pubmed.ncbi.nlm.nih.gov

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

10. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacological and pharmacokinetic properties of azithromycin (Zithromac), a novel 15-membered ring macrolide antibacterial agent]. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Azithromycin in lower respiratory tract infections. [2013]

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

Efficacy of azithromycin in reducing lower genital Ureaplasma urealyticum colonization in women at risk for preterm delivery. [2008]