Nirmatrelvir + Ritonavir for COVID-19 in Pregnancy

No longer recruiting at 31 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Pfizer

Must not be taking: CYP3A4 drugs, Antivirals

Disqualifiers: Hospitalization, Kidney impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and effectiveness of Paxlovid (a combination of nirmatrelvir and ritonavir) in treating mild or moderate COVID-19 in pregnant women compared to non-pregnant women. Participants will take Paxlovid orally every 12 hours for five days. The trial will include pregnant women in their second or third trimester and non-pregnant women with mild or moderate COVID-19. The study will last at least 34 days, with some participants continuing until delivery, and involves a mix of in-person and phone check-ins. This research will determine if Paxlovid is safe for these groups. As a Phase 1 trial, the study focuses on understanding how the treatment works in people, offering participants the opportunity to contribute to vital safety data.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that are heavily processed by the liver enzyme CYP3A4, as they are not safe to combine with the study drugs nirmatrelvir and ritonavir. It's important to discuss your current medications with the study team to see if any changes are needed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the two drugs in Paxlovid, nirmatrelvir and ritonavir, are safe for treating COVID-19 in pregnant women. Studies have found that pregnant women taking these drugs experience low rates of hospitalization and few serious side effects. Additional research supports the effectiveness and safety of these medicines for pregnant women with COVID-19. This combination of drugs has been used safely in pregnant patients, supporting its use in this trial.

Although this trial is in its early stages, evidence already indicates that these medicines are well-tolerated by pregnant women. The trial aims to learn more about how the drugs work in the body and their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for COVID-19?

Researchers are excited about Nirmatrelvir + Ritonavir for COVID-19 in pregnancy because these treatments offer a novel mechanism by targeting the virus's ability to replicate. Unlike the standard of care treatments like Remdesivir or monoclonal antibodies, which focus on other aspects of viral suppression, Nirmatrelvir is a protease inhibitor that specifically blocks an enzyme crucial for viral replication. This approach could provide an effective option for pregnant women, addressing their unique needs and potentially offering quicker results. Additionally, combining Nirmatrelvir with Ritonavir helps boost its effectiveness, making it a promising candidate in the fight against COVID-19 for this vulnerable population.

What evidence suggests that Paxlovid might be an effective treatment for COVID-19 in pregnancy?

Research shows that Paxlovid, a combination of nirmatrelvir and ritonavir, is safe and effective for treating mild to moderate COVID-19. This trial will study pregnant women in their second trimester, pregnant women in their third trimester, and non-pregnant women in separate cohorts. One study found that Paxlovid was effective during the Omicron wave, resulting in positive outcomes for pregnant women. Another study showed that pregnant women taking this treatment experienced low rates of hospitalization and side effects. These findings suggest that Paxlovid can help prevent severe COVID-19, making it a suitable option for pregnant women with the virus. ^{1 2 5 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for pregnant women in their second or third trimester with mild to moderate COVID-19, and non-pregnant individuals with the same condition. Participants should be expecting a healthy baby, not need hospitalization, have no major health risks that could affect the study or pregnancy outcome, and not be on certain medications.

Inclusion Criteria

You have mild-to-moderate COVID-19 and symptoms started within 5 days before the study.

You are pregnant with one baby and in the second trimester (14 to 27 weeks) or in the third trimester (28 to 34 weeks).

Otherwise healthy participants who are determined by medical history, physical examination, and clinical judgment to be appropriate for inclusion in the study

Exclusion Criteria

Current need for hospitalization or anticipated need for hospitalization in the clinical opinion of the site investigator

Prior/current major condition or illness of mother/fetus substantially increasing risk of study participation/completion or impacting pregnancy/fetal outcomes in investigator's judgement

You have moderate to severe kidney problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Paxlovid by mouth every 12 hours for 5 days

5 days

7 to 8 visits (2 to 3 in-person, 5 virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 6 months for pregnant participants, at least 34 days for others

Includes a visit at delivery for pregnant participants

What Are the Treatments Tested in This Trial?

Interventions

• Nirmatrelvir
• Ritonavir

Trial Overview The trial studies Paxlovid (nirmatrelvir plus ritonavir) in pregnant versus non-pregnant women with COVID-19. It aims to understand how this medication is processed by the body and its safety profile over a period of up to 6 months.

How Is the Trial Designed?

Group I: Cohort 3 Experimental Treatment 2 Interventions

Non-pregnant women

Group II: Cohort 2 Experimental Treatment 2 Interventions

Pregnant women in their third trimester

Group III: Cohort 1 Experimental Treatment 2 Interventions

Pregnant women in their second trimester

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

Approved in United States as Paxlovid for:

• Treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death

Approved in European Union as Paxlovid for:

• Treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a study of 437 pregnant patients, those who took nirmatrelvir-ritonavir for COVID-19 showed no significant differences in most obstetric and medical outcomes compared to those who did not take the medication, suggesting it is well-tolerated during pregnancy.

However, patients taking nirmatrelvir-ritonavir had higher rates of surgical site infections and preeclampsia, indicating the need for careful monitoring when prescribing this treatment to pregnant individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Nirmatrelvir-Ritonavir Use and Clinical Outcomes in Pregnant Patients With Coronavirus Disease 2019 (COVID-19). Toure, BB., Panakam, A., Johns, SL., et al.[2023]

Paxlovid, which combines nirmatrelvir and ritonavir, is an effective oral antiviral treatment for COVID-19, with nirmatrelvir specifically targeting the SARS-CoV-2 main protease to inhibit viral replication.

Ritonavir enhances the effectiveness of nirmatrelvir by slowing its metabolism, but it also poses a risk for drug interactions due to its role as a CYP3A4 inhibitor, necessitating careful management of other medications during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences. Azanza, JR., Mensa, J., González Del Castillo, J., et al.[2022]

Ritodrinum, a beta-sympathomimetic drug used to manage threatened premature labor, significantly increases cAMP levels in placentas from early gestation (6-8 weeks) by five times, indicating its potential to influence placental function during this period.

However, the drug has no effect on cAMP levels in term placentas, suggesting that its efficacy may be limited to earlier stages of pregnancy, which could impact how it is used in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro effect of ritodrinum on cAMP concentration in human placentas of different gestational age. Cemerikić, B., Genbacev, O., Sulović, V.[2013]

In a study of 264 hospitalized adults with severe comorbidities, Paxlovid (nirmatrelvir plus ritonavir) did not significantly reduce all-cause mortality or the duration of SARS-CoV-2 RNA clearance compared to standard treatment alone.

The incidence of adverse events was similar between the Paxlovid group and the standard treatment group, indicating that Paxlovid does not increase safety risks in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study. Liu, J., Pan, X., Zhang, S., et al.[2023]

In a survey of 35 pregnant individuals with breakthrough COVID-19, 51.4% were prescribed nirmatrelvir-ritonavir (Paxlovid), and 34.3% actually took the medication, with common side effects including dysgeusia (91.7%) and a 50% incidence of rebound symptoms.

Despite the lack of significant adverse outcomes reported, the most common reason for not taking the medication was the unknown risks associated with its use during pregnancy, highlighting the need for more research and better public health messaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nirmatrelvir-Ritonavir (Paxlovid) for Mild Coronavirus Disease 2019 (COVID-19) in Pregnancy and Lactation. Lin, CY., Cassidy, AG., Li, L., et al.[2023]

Transplacental betamethasone therapy did not improve the degree of complete atrioventricular block in fetuses with isolated congenital complete atrioventricular block (CCAVB), nor did it reduce the need for pacemaker implantation after birth.

However, among the patients treated with betamethasone, there was a potential reduction in the risk of developing myocardial disease, as indicated by better cardiac function in follow-up compared to those who did not receive the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of prenatally diagnosed isolated congenital complete atrioventricular block treated with transplacental betamethasone or ritodrine therapy. Hayashi, T., Kaneko, M., Kim, KS., et al.[2022]

In a study involving 38 pregnant women with recurrent preterm labor, oral sustained-release ritodrine at 320 mg/day achieved serum levels comparable to those from intravenous treatment, suggesting it could be an effective alternative.

The treatment was well-tolerated with no major maternal complications reported, indicating that oral ritodrine may be a safe option for managing preterm labor in selected cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral sustained-release ritodrine as a substitute for prolonged intravenous tocolysis. Gemer, O., Sassoon, E., Segal, S.[2019]

Paxlovid treatment in pregnant women with COVID-19 resulted in a shorter duration of symptoms (10.10 days) compared to those not treated (15.59 days), indicating its efficacy in managing COVID-19 during pregnancy.

No severe adverse events were reported from paxlovid use, suggesting it is safe for pregnant women, although there was a higher rate of caesarean deliveries in the treated group (76.92% vs. 42.86%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of nirmatrelvir-ritonavir use in pregnant women during the Omicron wave of the coronavirus disease 2019 pandemic. Lin, CW., Liang, YL., Chuang, MT., et al.[2023]

In the phase II/III EPIC-HR trial, the combination of nirmatrelvir and ritonavir (Paxlovid™) significantly reduced the risk of severe COVID-19 in symptomatic, unvaccinated adults with mild-to-moderate disease, showing lower rates of hospitalization or death compared to placebo.

Nirmatrelvir plus ritonavir is generally well tolerated, with most side effects being mild or moderate, indicating a favorable safety profile for this treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nirmatrelvir plus ritonavir in COVID-19: a profile of its use. Blair, HA.[2023]

In a study of 73 pregnant women with preterm labor, those receiving maintenance oral nifedipine therapy gained significantly more time before delivery (26.65 days) compared to the control group (16.14 days), indicating its efficacy in prolonging pregnancy.

While nifedipine therapy improved the gestational age at delivery (37.03 weeks vs. 35.1 weeks in controls), it did not reduce the recurrence of preterm labor episodes or enhance perinatal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral nifedipine maintenance therapy after acute intravenous tocolysis in preterm labor. Sayin, NC., Varol, FG., Balkanli-Kaplan, P., et al.[2013]

In a study of 167 cases of threatened premature birth, treatment with Fenoterol, either alone or in combination with Verapamil, resulted in 70-79% of newborns weighing over 2500 grams, indicating effective management of premature birth risks.

The treatments also successfully prolonged pregnancy for over 7 days in 70-76% of cases, and 61-64% of pregnancies reached a gestational age of 37 weeks or more, demonstrating the efficacy of these interventions in improving outcomes for at-risk pregnancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of premature labour and antagonization of the side effects of tocolytic therapy with verapamil (author's transl)]. Gummerus, M.[2013]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1876034123003349

Clinical outcomes of nirmatrelvir-ritonavir use in pregnant ... Conclusion. Our study showed that paxlovid was effective and safe for pregnant women during the Omicron wave of the COVID-19 pandemic. A higher proportion of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9709643/

Analysis of Clinical Outcomes of Pregnant Patients Treated ... Nirmatrelvir and ritonavir showed no significant reduction in hospitalization and deaths in a subgroup analysis of patients with at least 1 risk ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39948217/

Evaluating the safety and efficacy of nirmatrelvir-ritonavir ... Nirmatrelvir-ritonavir appears safe and effective for mild-to-moderate COVID-19 in pregnant women, with low rates of hospitalization and adverse maternal ...

4. academic.oup.com academic.oup.com/ofid/article/12/9/ofaf553/8246175

Real-World Effectiveness of Nirmatrelvir–Ritonavir Against ... This study aims to evaluate the real-world effectiveness of nirmatrelvir–ritonavir in preventing severe COVID-19-related outcomes, including ...

5. obgproject.com obgproject.com/2023/04/10/paxlovid-and-pregnancy-data-on-safety-and-clinical-outcomes/

Paxlovid and Pregnancy: Data on Safety and Clinical ... Findings of this case series support the safety and effectiveness of nirmatrelvir and ritonavir in pregnant patients with acute SARS-CoV-2.

6. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2799023

Analysis of Clinical Outcomes of Pregnant Patients Treated ... Results of this study suggest that pregnant patients with SARS-CoV-2 infection can be safely treated with nirmatrelvir and ritonavir.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9866309/

Paxlovid (Nirmatrelvir and Ritonavir) Use in Pregnant and ... Data on the safety of remdesivir use during pregnancy are inconclusive, and its use is based on assessing the benefit–risk profile [11].