Nirmatrelvir + Ritonavir for COVID-19 in Pregnancy

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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this clinical trial is to learn about how study medicine (Paxlovid, which contains nirmatrelvir and ritonavir) is changed and eliminated from the body, as well as its safety, and the extent to which side effects can be tolerated for treatment of pregnant women with mild or moderate COVID-19 compared to non-pregnant women with mild or moderate COVID-19. This study is seeking participants who: * are expecting a healthy baby and are in their second or third trimester pregnancy and have mild or moderate COVID-19 * are not pregnant and have mild or moderate COVID-19. All participants in this study will take Paxlovid by mouth every 12 hours for 5 days. We will study the experiences of people receiving the study medicine. This will help us decide if the study medicine is safe. All participants will take part in this study for at least 34 days; pregnant participants will take part until their delivery, so that the study duration may be up to 6 months, depending on their delivery date. During this time, participants will have 7to 8 visits and, if pregnant, a visit at delivery. Around 2 to 3 visits and the delivery visit will be done in person (at the clinic or at the participant's home). The other 5 visits may be done over the phone, unless in-person visit is necessary as decided by the doctor. Blood samples will be collected on the first 4 to 5 study visits (and at other study visits, if necessary).

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.

What data supports the effectiveness of the drug Nirmatrelvir + Ritonavir (Paxlovid) for COVID-19 in pregnancy?

Paxlovid, which includes nirmatrelvir and ritonavir, has been shown to reduce the risk of hospitalization or death by 89% in high-risk adults with COVID-19. In pregnant patients, it was well-tolerated and did not lead to intensive care unit admissions, although some experienced higher rates of surgical site infection and preeclampsia. ^{1 2 3 4 5}

Is Nirmatrelvir + Ritonavir (Paxlovid) safe for use in pregnancy?

Nirmatrelvir + Ritonavir (Paxlovid) has been used in pregnant individuals with COVID-19 and was generally well-tolerated, though some experienced taste changes and symptom rebound. There were no significant adverse outcomes reported, but more research is needed to fully understand its safety in pregnancy. ^{1 3 4 5 6}

How is the drug Nirmatrelvir + Ritonavir unique for treating COVID-19 in pregnancy?

Nirmatrelvir + Ritonavir (Paxlovid) is unique because it combines two antiviral drugs that work together to inhibit the virus's ability to replicate, which is different from treatments like Ritodrine used for preterm labor. This combination is specifically designed to target COVID-19, offering a novel approach compared to other treatments that may not directly address the virus's replication process. ^{7 8 9 10 11}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences. [2022]

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

Clinical outcomes of nirmatrelvir-ritonavir use in pregnant women during the Omicron wave of the coronavirus disease 2019 pandemic. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study. [2023]

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

Nirmatrelvir-Ritonavir (Paxlovid) for Mild Coronavirus Disease 2019 (COVID-19) in Pregnancy and Lactation. [2023]

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

Oral Nirmatrelvir-Ritonavir Use and Clinical Outcomes in Pregnant Patients With Coronavirus Disease 2019 (COVID-19). [2023]

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

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

7. Germany pubmed.ncbi.nlm.nih.gov

Oral nifedipine maintenance therapy after acute intravenous tocolysis in preterm labor. [2013]

8. Germany pubmed.ncbi.nlm.nih.gov

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

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

Outcome of prenatally diagnosed isolated congenital complete atrioventricular block treated with transplacental betamethasone or ritodrine therapy. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Oral sustained-release ritodrine as a substitute for prolonged intravenous tocolysis. [2019]

11. Germany pubmed.ncbi.nlm.nih.gov

In vitro effect of ritodrinum on cAMP concentration in human placentas of different gestational age. [2013]