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Conivaptan for the Reduction of Cerebral Edema in Intracerebral Hemorrhage: A Safety and Tolerability Study

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Abstract

Background

Perihematomal edema (PHE) growth in intracranial hemorrhage (ICH) is a biomarker for worse outcomes. Although the management of PHE is potentially beneficial for ICH patients, there is currently no proven clinical therapy that both reduces PHE and improves outcomes in this population.

Objective

To examine the safety and tolerability of conivaptan, a non-peptide vasopressin (AVP) receptor antagonist, for the management of PHE in ICH patients.

Methods

We performed a single-center, open-label, phase I study in seven patients with ICH at risk for developing PHE. Conivaptan (20 mg) was administered every 12 h for 2 days, along with the standard ICH management. Electrolyte levels, renal and cardiac function, and vital signs were monitored throughout treatment. Neurological status, ICH, and PHE volumes were assessed at study baseline, 24 h, 72 h, and 7 days from the first conivaptan administration, as well as at the 3-month follow-up.

Results

Conivaptan was well tolerated in our patients. We observed the expected increase in sodium levels following conivaptan administration (p = 0.01), with no change in cardiac or renal function. All patients survived to follow-up, and adverse event rates were comparable with those of the neurocritical care unit overall.

Conclusions

These data indicate that conivaptan can be safely administered to ICH patients and support further clinical investigation into the efficacy of this drug for ICH treatment.

Clinical Trial Registration

clinicaltrials.gov; NCT03000283, 22 December 2016.

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Author information

Authors and Affiliations

  1. John Nasseff Neuroscience Specialty Clinic, United Hospital Part of Allina Health, 310 Smith Ave N, MR 64440, Ritchie Building, Suite 440, Saint Paul, MN, 55102, USA

    Jesse J. Corry, Ganesh Asaithambi, Arif M. Shaik & Amy L. Castle

  2. Midwest Radiology, United Hospital Part of Allina Health, Saint Paul, MN, USA

    Jeffrey P. Lassig

  3. Neuroscience Research, United Hospital Part of Allina Health, Saint Paul, MN, USA

    Emily H. Marino, Bridget M. Ho, Nilanjana Banerji & Megan E. Tipps

  4. Department of Neurosciences, United Hospital Part of Allina Health, Saint Paul, MN, USA

    Jesse J. Corry, Ganesh Asaithambi, Arif M. Shaik, Jeffrey P. Lassig & Amy L. Castle

  5. Neuroscience Research, Abbott Northwestern Hospital, Minneapolis, MN, USA

    Emily H. Marino, Bridget M. Ho, Nilanjana Banerji & Megan E. Tipps

Authors
  1. Jesse J. Corry
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  2. Ganesh Asaithambi
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Contributions

JJC was the principal investigator on this study and responsible for the study conception. GA, AMS, JPL, EHM, and BMH contributed to study design. Material preparation and data collection were performed by JJC, GA, AMS, JPL, EHM, BMH, ALC, and NB. MET was responsible for data analysis. The first draft of the manuscript was written by JJC and MET, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jesse J. Corry.

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Funding

This work was supported by a grant from the United Hospital Medical Staff Education and Research Committee to Dr. Jesse Corry.

Conflict of interest

Jesse J. Corry, Ganesh Asaithambi, Arif M. Shaik, Jeffrey P. Lassig, Emily H. Marino, Bridget M. Ho, Amy L. Castle, Nilanjana Banerji, and Megan E. Tipps declare that they have no conflicts of interest that might be relevant to the contents of this article.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the national research committee (Quorum, QR#32036/1) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Quorum Review IRB (Protocol number NSJC-1601).

Informed consent

Consent to participate: All subjects signed informed consent forms after voluntarily agreeing to participate in the study. Consent for publication: As part of the informed consent for this study, all participants consented to the publication of their fully de-identified data.

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Corry, J.J., Asaithambi, G., Shaik, A.M. et al. Conivaptan for the Reduction of Cerebral Edema in Intracerebral Hemorrhage: A Safety and Tolerability Study. Clin Drug Investig 40, 503–509 (2020). https://doi.org/10.1007/s40261-020-00911-9

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  • DOI: https://doi.org/10.1007/s40261-020-00911-9

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