COVID-19NCT04582266
PK and Safety of Remdesivir for Treatment of COVID-19 in Pregnant and Non-Pregnant Women in the US
An observational study of COVID-19, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 sites in United States.
Trial summary
IMPAACT 2032 was a Phase IV prospective, open label, non-randomized opportunistic study. The objectives of this study were to describe the pharmacokinetic (PK) properties and safety of remdesivir (RDV) administered intravenously as part of clinical care among hospitalized pregnant and non-pregnant women of… Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- COVID-19
- What is being tested?
- Remdesivir
- Type of treatment
- Injection or infusion
- How many people
- 54 participants
- Where
- 10 sitesUnited States
- Study dates
- 31 Mar 2021to 13 Apr 2022
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Study population: This study was conducted among hospitalized pregnant and non-pregnant women receiving RDV for treatment of COVID-19 as part of their clinical care.
Who may be able to join
- Of legal age or otherwise able to provide independent informed consent or is unable to provide informed consent (e.g., impaired capacity) and a Legally Authorized Representative (LAR) is willing and able to provide written informed consent on behalf of the participant
- At study entry, viable intra-uterine pregnancy of any gestational age, based on medical records.
- At study entry, hospitalized AND has confirmed or suspected COVID-19, based on medical records.
- At study entry, receiving or expected to receive RDV for COVID-19 clinical care, as prescribed by the clinical care provider and documented in medical records.
- Of legal age or otherwise able to provide independent informed consent or is unable to provide informed consent (e.g., impaired capacity) and a Legally Authorized Representative (LAR) is willing and able to provide written informed consent on behalf of the participant
- At study entry, between 18 and 45 years of age, based on medical records and participant report.
Show all 10Show fewer
- Assigned female at birth and at study entry not taking cross-sex hormone therapy.
- At study entry, not suspected to be pregnant, based on participant report and/or investigator or designee determination.
- At study entry, hospitalized AND has confirmed or suspected COVID-19, based on medical records.
- At study entry, receiving or expected to receive RDV for COVID-19 clinical care, as prescribed by the clinical care provider and documented in medical records.
Who cannot join
- At study entry, has started or received the 4th RDV infusion.
- At study entry, evidence of post-menopausal status (medical or surgical), based on medical records and/or participant report.
- At study entry, any contraindications to RDV treatment for COVID-19, based on investigator or designee determination.
- Received or administered any disallowed medications within 48 hours prior to study entry.
- At study entry, has any other condition, that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Emory University School of Medicine (Site #: 5030)
Atlanta, Georgia, 30308
Johns Hopkins University NICHD CRS (Site #: 5092)
Baltimore, Maryland, 21287
Rush University Cook County Hospital NICHD CRS (Site #: 5083)
Chicago, Illinois, 60612
Lurie Children's Hospital of Chicago (LCH) CRS (Site #: 4001)
Chicago, Illinois, 60614
Childrens Hospital (U. Colorado, Denver) NICHD CRS (Site #: 5052)
Denver, Colorado, 80218-1088
Texas Children's Hospital (Site #: 5128)
Houston, Texas, 77030
David Geffen School of Medicine at UCLA (Site #: 5112)
Los Angeles, California, 90095
Pediatric Perinatal HIV Clinical Trials Unit (Site #: 5127)
Miami, Florida, 33136
Stony Brook University Medical Center (Site #: 5040)
Stony Brook, New York, 11794
Bronx-Lebanon Hospital Center (Site #: 5114)
The Bronx, New York, 10457
About this study
Official title: Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant and Non-Pregnant Women in the United States
IMPAACT 2032 was a Phase IV prospective, open label, non-randomized opportunistic study. The objectives of this study were to describe the pharmacokinetic (PK) properties and safety of remdesivir (RDV) administered intravenously as part of clinical care among hospitalized pregnant and non-pregnant women of childbearing potential with coronavirus disease of 2019 (COVID-19). RDV was provided and managed by the participant's treating physician and was not provided as part of this study.
Read the detailed description
IMPAACT 2032 was a Phase IV prospective, open label, non-randomized opportunistic study to evaluate the PK and safety of RDV when administered to pregnant and non-pregnant women of childbearing potential for treatment of COVID-19. Participants were pregnant and non-pregnant women hospitalized for COVID-19 who received daily RDV infusions, typically for 5 days but in some cases for up to 10 days, as part of their clinical care. RDV was provided and managed by the participants' treating physician and was not provided as a part of this study.
This study was comprised of two population-based arms: Arm 1 included pregnant women of any gestational age (GA) and Arm 2 included non-pregnant women of childbearing potential, who were between 18 and 45 years of age. The target sample size was 20 PK-evaluable participants per arm. Study sites were located in the United States.
Study procedures for this study were limited to data collection and blood specimens for PK. Except for PK sampling, study procedures were largely done via medical chart abstraction or remote contact/telemedicine visit. Collection of clinical and laboratory data started at 48 hours before the first infusion and continued through 4 weeks after the last infusion. In addition, data were collected at the time of delivery for participants in Arm 1, and limited data were also collected from the birth and newborn exam records of their infants. All participants were followed for safety through 4 weeks after the last infusion; Arm 1 participants who were still pregnant at that time had an additional follow-up at the time of delivery. If there was a gap in time between 4 weeks after the last infusion and delivery, no data were collected during that interval.
No formal statistical comparisons were made between Arm 1 and Arm 2 for primary and secondary objectives. Therefore, all analyses for primary and secondary outcome measures represent single arm evaluations.
- Conditions
- COVID-19
- Being tested
- Remdesivir
- Keywords
- COVID-19, Pregnancy
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemdesivirDrug
RDV was not provided as part of the study. Participants were administered RDV intravenously once daily for up to 10 days per clinical care.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Pregnant women hospitalized and receiving RDV for treatment of COVID-19. Receives: Drug: Remdesivir | |
| Arm 2 | Non-pregnant women of childbearing potential hospitalized and receiving RDV for treatment of COVID-19. Receives: Drug: Remdesivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 1
AUC calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Measured: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 1
t1/2 calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Measured: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 1
GS-441524 is a metabolite of remdesivir (RDV). Ctrough calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Measured: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
Safety Outcome: Proportion of Participants With Maternal Renal Adverse Event (AE) of Any Grade in Arm 1
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal renal AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Renal AEs were defined using the MedDRA system organ class term "Renal and urinary disorders" and high level grouping term "Renal and urinary tract investigations and urinalyses". The number of RDV infusions varied by participant.
Measured: First infusion through 7 Days post-last infusion
Safety Outcome: Proportion of Participants With Maternal Hepatic Adverse Event (AE) of Any Grade in Arm 1
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal hepatic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hepatic AEs were defined using the MedDRA system organ class term "Hepatobiliary disorders" and high level grouping term "Hepatobiliary investigations". The number of RDV infusions varied by participant.
Measured: First infusion through 7 Days post-last infusion
Safety Outcome: Proportion of Participants With Maternal Hematologic Adverse Event (AE) of Any Grade in Arm 1
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal hematologic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hematologic AEs were defined using the MedDRA system organ class term "Blood and lymphatic system disorders" and high level grouping term "Haematology investigations (incl blood groups)". The number of RDV infusions varied by participant.
Measured: First infusion through 7 Days post-last infusion
Safety Outcome: Proportion of Participants With Maternal Grade 3 or Higher Adverse Event (AE) in Arm 1
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one maternal grade 3 or higher adverse event through 4 weeks post last infusion and delivery, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Measured: First infusion through 4 Weeks post-last infusion and Delivery
Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 1
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal serious AE through 4 weeks post last infusion and delivery, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Measured: First infusion through 4 Weeks post-last infusion and Delivery
Safety Outcome: Proportion of Participants With Maternal Grade 3 or Higher Adverse Event (AE) Assessed as Related to Remdesivir (RDV) by the Clinical Management Committee (CMC) in Arm 1
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one maternal grade 3 or higher AE assessed as related to RDV by the CMC through 4 weeks post last infusion and delivery, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Measured: First infusion through 4 Weeks post-last infusion and Delivery
Safety Outcome: Proportion of Participants With Pregnancy Loss in Arm 1
We present the proportion of participants who had a pregnancy loss at delivery, bounded by an exact 95% confidence interval (CI).
Measured: Delivery
Safety Outcome: Proportion of Participants With Congenital Anomalies in Arm 1
We present the proportion of participants who had a live infant born with congenital anomalies at delivery, bounded by an exact 95% confidence interval (CI).
Measured: Delivery
Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 37 Weeks in Arm 1
We present the proportion of participants who had a live preterm birth defined as < 37 weeks, bounded by an exact 95% confidence interval (CI).
Measured: Delivery
Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 34 Weeks in Arm 1
We present the proportion of participants who had a live preterm birth defined as < 34 weeks, bounded by an exact 95% confidence interval (CI).
Measured: Delivery
Safety Outcome: Proportion of Participants With Small for Gestational Age, Defined as < 10th Percentile in Arm 1
We present the proportion of participants who a live born infant who was small for gestational age defined as < 10th percentile, bounded by an exact 95% confidence interval (CI).
Measured: Delivery
Safety Outcome: Mean Newborn Birth Weight in Arm 1
We present the newborn mean weight among the participants who had live born infant, bounded by a 95% confidence interval (CI) calculated using the t distribution.
Measured: Delivery
Safety Outcome: Mean Newborn Length in Arm 1
We present the newborn mean length among the participants who had a live born infant, bounded by a 95% confidence interval (CI) calculated using the t distribution.
Measured: Delivery
Safety Outcome: Mean Newborn Head Circumference in Arm 1
We present the newborn mean head circumference among the participants who had a live born infant, bounded by a 95% confidence interval (CI) calculated using the t distribution.
Measured: Delivery
Secondary outcomes (9)
PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 2
AUC calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Measured: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 2
t1/2 calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Measured: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 2
GS-441524 is a metabolite of remdesivir (RDV). Ctrough calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Measured: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
Safety Outcome: Proportion of Participants With Renal Adverse Event (AE) of Any Grade in Arm 2
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one renal AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Renal AEs were defined using the MedDRA system organ class term "Renal and urinary disorders" and high level grouping term "Renal and urinary tract investigations and urinalyses". The number of RDV infusions varied by participant.
Measured: First infusion through 7 Days post-last infusion
Safety Outcome: Proportion of Participants With Hepatic Adverse Event (AE) of Any Grade in Arm 2
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one hepatic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hepatic AEs were defined using the MedDRA system organ class term "Hepatobiliary disorders" and high level grouping term "Hepatobiliary investigations". The number of RDV infusions varied by participant.
Measured: First infusion through 7 Days post-last infusion
Safety Outcome: Proportion of Participants With Hematologic Adverse Event (AE) of Any Grade in Arm 2
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one hematologic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hematologic AEs were defined using the MedDRA system organ class term "Blood and lymphatic system disorders" and high level grouping term "Haematology investigations (incl blood groups)". The number of RDV infusions varied by participant.
Measured: First infusion through 7 Days post-last infusion
Safety Outcome: Proportion of Participants With Grade 3 or Higher Adverse Event (AE) in Arm 2
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one grade 3 or higher AE through 4 weeks post last infusion, bounded by an exact 95% confidence interval (CI).
Measured: First infusion through 4 Weeks post-last infusion
Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 2
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one serious AE through 4 weeks post last infusion, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Measured: First infusion through 4 Weeks post-last infusion
Safety Outcome: Proportion of Participants With Grade 3 or Higher Adverse Event (AE) Assessed as Related to Remdesivir (RDV) by the Clinical Management Committee (CMC) in Arm 2
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one grade 3 or higher AE as related to RDV by the CMC through 4 weeks post last infusion, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Measured: First infusion through 4 Weeks post-last infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2020
- Study start31 Mar 2021
- Primary completion13 Apr 2022
- Study completion13 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Gilead Sciences
- Responsible party
- Sponsor
- Investigators
- Mark Mirochnick, MD, Study chair, Department of Pediatrics, Boston University Chobanian and Avedisian School of MedicineDiana Clarke, PharmD, Study chair, Pediatric Infectious Diseases, Boston Medical CenterBrookie Best, PharmD, MAS, Study chair, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04582266
- Sponsor's protocol ID
- IMPAACT 2032
- Other IDs
- DAIDS Study ID 38746
- Status last verified
- May 2023
- First submitted
- 8 Oct 2020
- Last updated
- 9 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification.
Publications
Brooks KM, Baltrusaitis K, Clarke DF, Nachman S, Jao J, Purswani MU, Agwu A, Beneri C, Deville JG, Powis KM, Stek AM, Eke AC, Shapiro DE, Capparelli E, Greene E, George K, Yin DE, Jean-Philippe P, Chakhtoura N, Bone F, Bacon K, Johnston B, Reding C, Kersey K, Humeniuk R, Best BM, Mirochnick M, Momper JD; IMPAACT 2032 Study Team. Pharmacokinetics and Safety of Remdesivir in Pregnant and Nonpregnant Women With COVID-19: Results From IMPAACT 2032. J Infect Dis. 2024 Oct 16;230(4):878-888. doi: 10.1093/infdis/jiae298.
PubMed 38839047
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant and Non-Pregnant Women in the United States
- ClinicalTrials.gov ID
- NCT04582266
- Acronym / sponsor ID
- IMPAACT 2032
- Conditions
- COVID-19
- Keywords
- COVID-19, Pregnancy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Gilead Sciences
- Study start
- 31 Mar 2021 (actual)
- Primary completion
- 13 Apr 2022 (actual)
- Study completion
- 13 Apr 2022 (actual)
- First posted
- 9 Oct 2020 (actual)
- Results
- Posted 9 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
IMPAACT 2032 was a Phase IV prospective, open label, non-randomized opportunistic study. The objectives of this study were to describe the pharmacokinetic (PK) properties and safety of remdesivir (RDV) administered intravenously as part of clinical care among hospitalized pregnant and non-pregnant women of childbearing potential with coronavirus disease of 2019 (COVID-19). RDV was provided and managed by the participant's treating physician and was not provided as part of this study.
Detailed description
IMPAACT 2032 was a Phase IV prospective, open label, non-randomized opportunistic study to evaluate the PK and safety of RDV when administered to pregnant and non-pregnant women of childbearing potential for treatment of COVID-19. Participants were pregnant and non-pregnant women hospitalized for COVID-19 who received daily RDV infusions, typically for 5 days but in some cases for up to 10 days, as part of their clinical care. RDV was provided and managed by the participants' treating physician and was not provided as a part of this study.
This study was comprised of two population-based arms: Arm 1 included pregnant women of any gestational age (GA) and Arm 2 included non-pregnant women of childbearing potential, who were between 18 and 45 years of age. The target sample size was 20 PK-evaluable participants per arm. Study sites were located in the United States.
Study procedures for this study were limited to data collection and blood specimens for PK. Except for PK sampling, study procedures were largely done via medical chart abstraction or remote contact/telemedicine visit. Collection of clinical and laboratory data started at 48 hours before the first infusion and continued through 4 weeks after the last infusion. In addition, data were collected at the time of delivery for participants in Arm 1, and limited data were also collected from the birth and newborn exam records of their infants. All participants were followed for safety through 4 weeks after the last infusion; Arm 1 participants who were still pregnant at that time had an additional follow-up at the time of delivery. If there was a gap in time between 4 weeks after the last infusion and delivery, no data were collected during that interval.
No formal statistical comparisons were made between Arm 1 and Arm 2 for primary and secondary objectives. Therefore, all analyses for primary and secondary outcome measures represent single arm evaluations.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | – | Drug: RemdesivirPregnant women hospitalized and receiving RDV for treatment of COVID-19. |
| Arm 2 | – | Drug: RemdesivirNon-pregnant women of childbearing potential hospitalized and receiving RDV for treatment of COVID-19. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- This study was conducted among hospitalized pregnant and non-pregnant women receiving RDV for treatment of COVID-19 as part of their clinical care.
Key inclusion criteria (10 listed)
- Of legal age or otherwise able to provide independent informed consent or is unable to provide informed consent (e.g., impaired capacity) and a Legally Authorized Representative (LAR) is willing and able to provide written informed consent on behalf of the participant
- At study entry, viable intra-uterine pregnancy of any gestational age, based on medical records.
- At study entry, hospitalized AND has confirmed or suspected COVID-19, based on medical records.
- At study entry, receiving or expected to receive RDV for COVID-19 clinical care, as prescribed by the clinical care provider and documented in medical records.
- Of legal age or otherwise able to provide independent informed consent or is unable to provide informed consent (e.g., impaired capacity) and a Legally Authorized Representative (LAR) is willing and able to provide written informed consent on behalf of the participant
Key exclusion criteria (5 listed)
- At study entry, has started or received the 4th RDV infusion.
- At study entry, evidence of post-menopausal status (medical or surgical), based on medical records and/or participant report.
- At study entry, any contraindications to RDV treatment for COVID-19, based on investigator or designee determination.
- Received or administered any disallowed medications within 48 hours prior to study entry.
- At study entry, has any other condition, that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RemdesivirRDV was not provided as part of the study. Participants were administered RDV intravenously once daily for up to 10 days per clinical care. | Drug | Arm 1, Arm 2 |
Primary outcome
PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 1
Time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
AUC calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 1
Time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
t1/2 calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 1
Time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
GS-441524 is a metabolite of remdesivir (RDV). Ctrough calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Safety Outcome: Proportion of Participants With Maternal Renal Adverse Event (AE) of Any Grade in Arm 1
Time frame: First infusion through 7 Days post-last infusion
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal renal AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Renal AEs were defined using the MedDRA system organ class term "Renal and urinary disorders" and high level grouping term "Renal and urinary tract investigations and urinalyses". The number of RDV infusions varied by participant.
Safety Outcome: Proportion of Participants With Maternal Hepatic Adverse Event (AE) of Any Grade in Arm 1
Time frame: First infusion through 7 Days post-last infusion
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal hepatic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hepatic AEs were defined using the MedDRA system organ class term "Hepatobiliary disorders" and high level grouping term "Hepatobiliary investigations". The number of RDV infusions varied by participant.
Safety Outcome: Proportion of Participants With Maternal Hematologic Adverse Event (AE) of Any Grade in Arm 1
Time frame: First infusion through 7 Days post-last infusion
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal hematologic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hematologic AEs were defined using the MedDRA system organ class term "Blood and lymphatic system disorders" and high level grouping term "Haematology investigations (incl blood groups)". The number of RDV infusions varied by participant.
Safety Outcome: Proportion of Participants With Maternal Grade 3 or Higher Adverse Event (AE) in Arm 1
Time frame: First infusion through 4 Weeks post-last infusion and Delivery
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one maternal grade 3 or higher adverse event through 4 weeks post last infusion and delivery, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 1
Time frame: First infusion through 4 Weeks post-last infusion and Delivery
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal serious AE through 4 weeks post last infusion and delivery, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Safety Outcome: Proportion of Participants With Maternal Grade 3 or Higher Adverse Event (AE) Assessed as Related to Remdesivir (RDV) by the Clinical Management Committee (CMC) in Arm 1
Time frame: First infusion through 4 Weeks post-last infusion and Delivery
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one maternal grade 3 or higher AE assessed as related to RDV by the CMC through 4 weeks post last infusion and delivery, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Safety Outcome: Proportion of Participants With Pregnancy Loss in Arm 1
Time frame: Delivery
We present the proportion of participants who had a pregnancy loss at delivery, bounded by an exact 95% confidence interval (CI).
Safety Outcome: Proportion of Participants With Congenital Anomalies in Arm 1
Time frame: Delivery
We present the proportion of participants who had a live infant born with congenital anomalies at delivery, bounded by an exact 95% confidence interval (CI).
Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 37 Weeks in Arm 1
Time frame: Delivery
We present the proportion of participants who had a live preterm birth defined as < 37 weeks, bounded by an exact 95% confidence interval (CI).
Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 34 Weeks in Arm 1
Time frame: Delivery
We present the proportion of participants who had a live preterm birth defined as < 34 weeks, bounded by an exact 95% confidence interval (CI).
Safety Outcome: Proportion of Participants With Small for Gestational Age, Defined as < 10th Percentile in Arm 1
Time frame: Delivery
We present the proportion of participants who a live born infant who was small for gestational age defined as < 10th percentile, bounded by an exact 95% confidence interval (CI).
Safety Outcome: Mean Newborn Birth Weight in Arm 1
Time frame: Delivery
We present the newborn mean weight among the participants who had live born infant, bounded by a 95% confidence interval (CI) calculated using the t distribution.
Safety Outcome: Mean Newborn Length in Arm 1
Time frame: Delivery
We present the newborn mean length among the participants who had a live born infant, bounded by a 95% confidence interval (CI) calculated using the t distribution.
Safety Outcome: Mean Newborn Head Circumference in Arm 1
Time frame: Delivery
We present the newborn mean head circumference among the participants who had a live born infant, bounded by a 95% confidence interval (CI) calculated using the t distribution.
9 secondary outcomes
PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 2
Time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 2
Time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 2
Time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
Safety Outcome: Proportion of Participants With Renal Adverse Event (AE) of Any Grade in Arm 2
Time frame: First infusion through 7 Days post-last infusion
Safety Outcome: Proportion of Participants With Hepatic Adverse Event (AE) of Any Grade in Arm 2
Time frame: First infusion through 7 Days post-last infusion
Safety Outcome: Proportion of Participants With Hematologic Adverse Event (AE) of Any Grade in Arm 2
Time frame: First infusion through 7 Days post-last infusion
Safety Outcome: Proportion of Participants With Grade 3 or Higher Adverse Event (AE) in Arm 2
Time frame: First infusion through 4 Weeks post-last infusion
Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 2
Time frame: First infusion through 4 Weeks post-last infusion
Safety Outcome: Proportion of Participants With Grade 3 or Higher Adverse Event (AE) Assessed as Related to Remdesivir (RDV) by the Clinical Management Committee (CMC) in Arm 2
Time frame: First infusion through 4 Weeks post-last infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38839047Brooks KM, Baltrusaitis K, Clarke DF, Nachman S, Jao J, Purswani MU, Agwu A, Beneri C, Deville JG, Powis KM, Stek AM, Eke AC, Shapiro DE, Capparelli E, Greene E, George K, Yin DE, Jean-Philippe P, Chakhtoura N, Bone F, Bacon K, Johnston B, Reding C, Kersey K, Humeniuk R, Best BM, Mirochnick M, Momper JD; IMPAACT 2032 Study Team. Pharmacokinetics and Safety of Remdesivir in Pregnant and Nonpregnant Women With COVID-19: Results From IMPAACT 2032. J Infect Dis. 2024 Oct 16;230(4):878-888. doi: 10.1093/infdis/jiae298.
- DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017Link provided by the sponsor.
- Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie results in the publication, after deidentification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Mirochnick, MD study chair
Department of Pediatrics, Boston University Chobanian and Avedisian School of Medicine
Diana Clarke, PharmD study chair
Pediatric Infectious Diseases, Boston Medical Center
Brookie Best, PharmD, MAS study chair
University of California, San Diego
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 1 (time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04582266, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2023.