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NCT04582266

PK and Safety of Remdesivir for Treatment of COVID-19 in Pregnant and Non-Pregnant Women in the US

Completed Results posted Last updated 9 June 2023
What this trial tests

trial testing Remdesivir in COVID-19 in 54 participants. Completed in 13 April 2022.

Timeline
31 March 2021
Primary endpoint
13 April 2022
13 April 2022

Quick facts

Lead sponsorNational Institute of Allergy and Infectious Diseases (NIAID)
StatusCompleted
Study typeOBSERVATIONAL
Enrollment54
Start date31 March 2021
Primary completion13 April 2022
Estimated completion13 April 2022
Sites10 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Eligibility, female only, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 1 Primary · 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.

GroupValue95% CI
Arm 11246.57915.71 – 1696.99
PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 1 Primary · 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.

GroupValue95% CI
Arm 11.010.87 – 1.17
PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 1 Primary · 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.

GroupValue95% CI
Arm 151.644.7 – 59.6
Safety Outcome: Proportion of Participants With Maternal Renal Adverse Event (AE) of Any Grade in Arm 1 Primary · 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.

GroupValue95% CI
Arm 100 – 0.15
Safety Outcome: Proportion of Participants With Maternal Hepatic Adverse Event (AE) of Any Grade in Arm 1 Primary · 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.

GroupValue95% CI
Arm 10.040.00 – 0.22
Safety Outcome: Proportion of Participants With Maternal Hematologic Adverse Event (AE) of Any Grade in Arm 1 Primary · 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.

GroupValue95% CI
Arm 10.300.13 – 0.53
Safety Outcome: Proportion of Participants With Maternal Grade 3 or Higher Adverse Event (AE) in Arm 1 Primary · 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

GroupValue95% CI
Arm 10.680.45 – 0.86
Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 1 Primary · 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.

GroupValue95% CI
Arm 10.330.13 – 0.59
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 Primary · 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

GroupValue95% CI
Arm 10.000.00 – 0.21
Safety Outcome: Proportion of Participants With Pregnancy Loss in Arm 1 Primary · Delivery

We present the proportion of participants who had a pregnancy loss at delivery, bounded by an exact 95% confidence interval (CI).

GroupValue95% CI
Arm 10.060.00 – 0.29
Safety Outcome: Proportion of Participants With Congenital Anomalies in Arm 1 Primary · 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).

GroupValue95% CI
Arm 10.000.00 – 0.21
Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 37 Weeks in Arm 1 Primary · 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).

GroupValue95% CI
Arm 10.250.07 – 0.52

Adverse events — posted to ClinicalTrials.gov

Time frame: Enrolled women in Arm 1 were followed for 4 weeks after the last RDV infusion and at delivery. Enrolled women in Arm 2 were followed for 4 weeks after the last RDV infusion.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm 1
Serious: 7/25 (28%)
Deaths: 0/25
Arm 2
Serious: 4/28 (14%)
Deaths: 0/28

Serious adverse events (13 terms)

ReactionSystemArm 1Arm 2
Respiratory failureRespiratory, thoracic and mediastinal disorders
Foetal heart rate deceleration abnormalityCardiac disorders
AstheniaGeneral disorders
COVID-19 pneumoniaInfections and infestations
Haemoglobin decreasedInvestigations
Foetal deathPregnancy, puerperium and perinatal conditions
Gestational hypertensionPregnancy, puerperium and perinatal conditions
Superimposed pre-eclampsiaPregnancy, puerperium and perinatal conditions
Substance-induced psychotic disorderPsychiatric disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Respiratory distressRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
Other adverse events (48 terms — click to expand)

ReactionSystemArm 1Arm 2
DyspnoeaRespiratory, thoracic and mediastinal disorders
Haemoglobin decreasedInvestigations
Lymphocyte count decreasedInvestigations
COVID-19 pneumoniaInfections and infestations
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
LymphopeniaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
Blood glucose increasedInvestigations
Oxygen saturation decreasedInvestigations
HypoxiaRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
AnaemiaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
BradycardiaCardiac disorders
Left ventricular dilatationCardiac disorders
Sinus bradycardiaCardiac disorders
DysphagiaGastrointestinal disorders
Obstructive pancreatitisGastrointestinal disorders
AstheniaGeneral disorders
Chest painGeneral disorders
FatigueGeneral disorders
Infusion site oedemaGeneral disorders
Infusion site painGeneral disorders
PyrexiaGeneral disorders
PneumoniaInfections and infestations
Pneumonia klebsiellaInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Blood bicarbonate decreasedInvestigations
Blood pressure increasedInvestigations
Glomerular filtration rate decreasedInvestigations
International normalised ratio increasedInvestigations
Lipase increasedInvestigations
Prothrombin time prolongedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
HypervolaemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
High risk pregnancyPregnancy, puerperium and perinatal conditions

Most-reported serious reactions: Respiratory failure, Foetal heart rate deceleration abnormality, Asthenia, COVID-19 pneumonia, Haemoglobin decreased, Foetal death, Gestational hypertension, Superimposed pre-eclampsia.

Data from ClinicalTrials.gov NCT04582266 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Remdesivir for treatment of COVID-19; an updated systematic review and meta-analysis.
    Rezagholizadeh A, Khiali S, Sarbakhsh P, Entezari-Maleki T. · · 2021 · cited 85× · PMID 33549577 · DOI 10.1016/j.ejphar.2021.173926
  2. Therapeutics for COVID-19 and post COVID-19 complications: An update.
    Basu D, Chavda VP, Mehta AA. · · 2022 · cited 44× · PMID 35136858 · DOI 10.1016/j.crphar.2022.100086
  3. The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy.
    Kouhpayeh S, Shariati L, Boshtam M, Rahimmanesh I, et al · · 2021 · cited 26× · PMID 34064039 · DOI 10.3390/ijms22115438
  4. Docking and <i>in silico</i> toxicity assessment of <i>Arthrospira</i> compounds as potential antiviral agents against SARS-CoV-2.
    Petit L, Vernès L, Cadoret JP. · · 2021 · cited 22× · PMID 33776210 · DOI 10.1007/s10811-021-02372-9
  5. Sex-tailored pharmacology and COVID-19: Next steps towards appropriateness and health equity.
    Spini A, Giudice V, Brancaleone V, Morgese MG, et al · · 2021 · cited 21× · PMID 34454035 · DOI 10.1016/j.phrs.2021.105848
  6. Maternal endothelial dysfunction in HIV-associated preeclampsia comorbid with COVID-19: a review.
    Naidoo N, Moodley J, Naicker T. · · 2021 · cited 19× · PMID 33469197 · DOI 10.1038/s41440-020-00604-y
  7. Therapeutic dilemmas in addressing SARS-CoV-2 infection: Favipiravir versus Remdesivir.
    Negru PA, Radu AF, Vesa CM, Behl T, et al · · 2022 · cited 18× · PMID 35131656 · DOI 10.1016/j.biopha.2022.112700
  8. Repurpose but also (nano)-reformulate! The potential role of nanomedicine in the battle against SARS-CoV2.
    Tammam SN, El Safy S, Ramadan S, Arjune S, et al · · 2021 · cited 13× · PMID 34293319 · DOI 10.1016/j.jconrel.2021.07.028

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing