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Clinical trial of extended-release felodipine in pediatric essential hypertension

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Abstract.

Essential hypertension in pediatric patients may require pharmacological treatment. There is a need for efficacious, safe, and well-tolerated antihypertensive agents with a once-a-day dosing regimen in children and adolescents. The aim of the trial was to evaluate the dose-response and tolerability of the dihydropyridine calcium channel blocker, felodipine extended-release tablets (felodipine ER), given once daily to pediatric patients with essential hypertension. A randomized double-blind, parallel-group, multi-center clinical study comparing felodipine ER (2.5, 5, or 10 mg once daily) and placebo was performed on pediatric patients with a baseline systolic (SBP) or diastolic blood pressure (DBP) above the 95th percentile for age, sex, and height. Of 133 randomized patients, 128 (96.2%) completed the 3 weeks of double-blind treatment. The study population included 50% children 6–12 years of age or Tanner stage ≤3, 39% black, and 40% female patients. All doses of felodipine ER and placebo decreased both SBP and DBP. The 5-mg dose of felodipine ER resulted in a significant decline in trough sitting, standing, and supine DBP (placebo-adjusted, −4.6, −5.06, and −5.05 mmHg, respectively, P<0.05) compared with placebo. However, there was no significant decline in SBP. The 2.5- and 10-mg doses showed no significant differences compared with placebo in lowering BP. The effect of felodipine ER was comparable in patient subgroups by age, race, and gender. The drug was well tolerated. The study failed to show a dose response of felodipine ER in pediatric patients with essential hypertension. This finding might be explained in part by the limitations of study design. The spectrum of side effects in pediatric patients was comparable with that in adults, except for a lower incidence of peripheral edema. Further studies are needed to clarify the role of felodipine ER in the management of children and adolescents with essential hypertension.

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Acknowledgement.

The authors would like to thank Michaelene Llewellyn and Scott Rosenberger for their efforts and support in managing this multi-center clinical trial.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Nephrology, Schneider Children's Hospital of the North Shore-LIJ Health System, New Hyde Park, NY 11040, USA

    Howard Trachtman & Rachel Frank

  2. Children's Hospital and Pediatric Clinical Trials International, Columbus, Ohio, USA

    John D. Mahan

  3. Department of Pediatrics, Hermann Hospital, Houston, Texas, USA

    Ronald Portman

  4. Children's Hospital of the King's Daughters, Norfolk, Virginia, USA

    Irene Restaino

  5. Children's Hospital of Michigan, Detroit, Michigan, USA

    Tej K. Matoo

  6. AstraZeneca, Wayne, Pennsylvania, USA

    Conrad Tou & Michael Klibaner

  7. Division of Nephrology, Room SCH 365, Schneider Children's Hospital, 269–01 76th Avenue, New Hyde Park, NY 11040, USA

    Howard Trachtman

Authors
  1. Howard Trachtman
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  2. Rachel Frank
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  3. John D. Mahan
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  4. Ronald Portman
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  5. Irene Restaino
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  6. Tej K. Matoo
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  7. Conrad Tou
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  8. Michael Klibaner
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Corresponding author

Correspondence to Howard Trachtman.

Additional information

The complete list of investigators and sites for the Plendil Pediatric Clinical Trial is listed in the Appendix

Appendix

Appendix

List of local principal investigators and participating sites where patients were enrolled in the study: Mazan Arar (transferred from Ihasan Elshibabi), University Hospital-Children's Kidney Center, San Antonio, Tex.; Noosha Baqi, State University of New York Health Science Center, Brooklyn, N.Y.; Mark Benfield (transferred from Judith Lynn Pugh), Children's Hospital of Alabama, Birmingham, Ala.; Stuart Berger, Children's Hospital of Wisconsin, Madison, Wis.; Robert J. Cunningham, Cleveland Clinic Foundation, Cleveland, Ohio; Ian G. Dresner, Children's Hospital Medical Center of Akron, Akron, Ohio; Bonita Falkner, Thomas Jefferson University, Philadelphia, Pa.; Eduardo Garin, University of South Florida Ambulatory Medical Clinics, Tampa, Fla.; Jens Goebel, University of Kentucky, Lexington, Ky.; Coral D. Hanevold, Children's Medical Center, Augusta, Ga.; Randall Jenkins, Norwest Pediatric Kidney Specialists, Portland, Ore.; Pedro Jose, Georgetown University Medical Center, Washington D.C.; Vijay Kusnoor, South East Texas Cardiology Associates, Beaumont, Tex.; John Mahan, Clinical Study Center, Columbus, Ohio; Tej Matoo, Children's Hospital of Michigan, Detroit, Mich.; Joel Melnick, Children's Memorial Hospital, Chicago, Ill.; Susan R. Mendley, University of Maryland Medical School, Baltimore, Md.; Kenneth Miller, Nephrology and Hypertension Consultants, Park Ridge, Ill.; Shashi Nagaraj, Wake Forest University, Winston-Salem, N.C.; Ronald Portman, Hermann Hospital, Houston, Tex.; Jorge A. Ramirez, Nemours Children's Clinic-Orlando, Orlando, Fla.; Irene Restaino, Children's Hospital of the King's Daughters, Norfolk, Va.; George A. Richard, Shands Hospital, Gainesville, Fla.; Ari Simckes, Children's Mercy Hospital, Kansas City, Mo.; W. Frank Tenny (transferred from Abdullah Sakarcan), Louisiana State University Health Sciences Center, Shreveport, La.; Frederick Strife, Children's Hospital Medical Center, Cincinnati, Ohio; Howard Trachtman, Schneider Children's Hospital, New Hyde Park, N.Y.; Lynn Weiss, Robert Wood Johnson Medical School, New Brunswick, N.J.; Matti Vehaskari, Children's Hospital, New Orleans, La.; Shefali Vyas (transferred from Andrea L. Zuckerman), New York Medical Center, Valhalla, N.Y.

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Trachtman, H., Frank, R., Mahan, J.D. et al. Clinical trial of extended-release felodipine in pediatric essential hypertension. Pediatr Nephrol 18, 548–553 (2003). https://doi.org/10.1007/s00467-003-1134-0

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  • DOI: https://doi.org/10.1007/s00467-003-1134-0

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