Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: Report of a prospective (Phase II) multicenter study

B. Timothy Baxter, William H. Pearce, Eugene A. Waltke, Fred N. Littooy, John W. Hallett, K. Craig Kent, Gilbert R. Upchurch, Elliot L. Chaikof, Joseph L Mills, Beverly Fleckten, G. Matt Longo, Jason K. Lee, Robert W. Thompson

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Abstract

Background: The primary purpose of this study was to evaluate compliance, side effects, and safety associated with prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms (AAAs). A secondary goal was to determine how treatment with doxycycline influences circulating levels of matrix metalloproteinase-9 (MMP-9) in this patient population. Methods: Thirty-six patients with AAAs (30 men and 6 women; mean age, 69 ± 1 years) were enrolled into a 6-month phase II study to evaluate treatment with doxycycline (100 mg orally twice a day). Aneurysm size was measured before and after treatment, and compliance and side effects were monitored. Plasma levels of doxycycline were measured midway through the study, and plasma MMP-9 concentrations were measured at baseline, 3 months, and 6 months. Results: Thirty-three of the 36 patients (92%) completed 6 months of doxycycline treatment. Significant treatment-related side effects occurred in five patients (13.9%), including three with cutaneous photosensitivity reactions (8.3%), one with tooth discoloration (2.8%), and one with yeast infection (2.8%). A high rate of compliance with treatment was seen, despite minor but frequent side effects, including nonspecific gastrointestinal symptoms (25%), easily managed episodes of photosensitivity (22.2%), and reversible tooth discoloration (5.5%). The mean plasma doxycycline level after 3 months was 4.62 ± 0.68 ug/mL (median, 3.64 μg/mL; range, 1.31 to 14.39 μg/mL; n = 23 patients). No significant change was seen in AAA diameter (42.7 ± 1.3 mm at 6 months versus 41.0 ± 0.9 mm at baseline), and the overall rate of AAA expansion was 0.63% ± 0.25% per month. The mean plasma MMP-9 level (n = 19 patients) was elevated at baseline (118.9 ± 37.9 ng/mL; upper limit of normal, 85 ng/mL) but subsequently decreased to 83.8 ± 32.9 ng/mL at 3 months (not signifcant versus baseline) and to 66.4 ± 24.2 ng/mL at 6 months (P = .022 versus baseline). Only 21% of patients had an elevated level of plasma MMP-9 after 6 months of treatment compared with 47% at baseline (P < .05). Conclusion: Prolonged administration of doxycycline is safe and well tolerated by patients with small asymptomatic AAAs and is associated with a gradual reduction in plasma MMP-9 levels. Further studies are needed to evaluate the long-term effects of doxycycline on the rate and extent of aneurysm growth and the potential use of plasma MMP-9 levels as a biomarker of aneurysm disease progression.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalJournal of Vascular Surgery
Volume36
Issue number1
DOIs
StatePublished - Jul 2002

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Doxycycline
Abdominal Aortic Aneurysm
Multicenter Studies
Matrix Metalloproteinase 9
Tooth Discoloration
Aneurysm
Therapeutics
Compliance
Disease Progression
Yeasts
Biomarkers
Safety
Skin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

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Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms : Report of a prospective (Phase II) multicenter study. / Baxter, B. Timothy; Pearce, William H.; Waltke, Eugene A.; Littooy, Fred N.; Hallett, John W.; Kent, K. Craig; Upchurch, Gilbert R.; Chaikof, Elliot L.; Mills, Joseph L; Fleckten, Beverly; Longo, G. Matt; Lee, Jason K.; Thompson, Robert W.

In: Journal of Vascular Surgery, Vol. 36, No. 1, 07.2002, p. 1-12.

Research output: Contribution to journalArticle

Baxter, BT, Pearce, WH, Waltke, EA, Littooy, FN, Hallett, JW, Kent, KC, Upchurch, GR, Chaikof, EL, Mills, JL, Fleckten, B, Longo, GM, Lee, JK & Thompson, RW 2002, 'Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: Report of a prospective (Phase II) multicenter study', Journal of Vascular Surgery, vol. 36, no. 1, pp. 1-12. https://doi.org/10.1067/mva.2002.125018
Baxter, B. Timothy ; Pearce, William H. ; Waltke, Eugene A. ; Littooy, Fred N. ; Hallett, John W. ; Kent, K. Craig ; Upchurch, Gilbert R. ; Chaikof, Elliot L. ; Mills, Joseph L ; Fleckten, Beverly ; Longo, G. Matt ; Lee, Jason K. ; Thompson, Robert W. / Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms : Report of a prospective (Phase II) multicenter study. In: Journal of Vascular Surgery. 2002 ; Vol. 36, No. 1. pp. 1-12.
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abstract = "Background: The primary purpose of this study was to evaluate compliance, side effects, and safety associated with prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms (AAAs). A secondary goal was to determine how treatment with doxycycline influences circulating levels of matrix metalloproteinase-9 (MMP-9) in this patient population. Methods: Thirty-six patients with AAAs (30 men and 6 women; mean age, 69 ± 1 years) were enrolled into a 6-month phase II study to evaluate treatment with doxycycline (100 mg orally twice a day). Aneurysm size was measured before and after treatment, and compliance and side effects were monitored. Plasma levels of doxycycline were measured midway through the study, and plasma MMP-9 concentrations were measured at baseline, 3 months, and 6 months. Results: Thirty-three of the 36 patients (92{\%}) completed 6 months of doxycycline treatment. Significant treatment-related side effects occurred in five patients (13.9{\%}), including three with cutaneous photosensitivity reactions (8.3{\%}), one with tooth discoloration (2.8{\%}), and one with yeast infection (2.8{\%}). A high rate of compliance with treatment was seen, despite minor but frequent side effects, including nonspecific gastrointestinal symptoms (25{\%}), easily managed episodes of photosensitivity (22.2{\%}), and reversible tooth discoloration (5.5{\%}). The mean plasma doxycycline level after 3 months was 4.62 ± 0.68 ug/mL (median, 3.64 μg/mL; range, 1.31 to 14.39 μg/mL; n = 23 patients). No significant change was seen in AAA diameter (42.7 ± 1.3 mm at 6 months versus 41.0 ± 0.9 mm at baseline), and the overall rate of AAA expansion was 0.63{\%} ± 0.25{\%} per month. The mean plasma MMP-9 level (n = 19 patients) was elevated at baseline (118.9 ± 37.9 ng/mL; upper limit of normal, 85 ng/mL) but subsequently decreased to 83.8 ± 32.9 ng/mL at 3 months (not signifcant versus baseline) and to 66.4 ± 24.2 ng/mL at 6 months (P = .022 versus baseline). Only 21{\%} of patients had an elevated level of plasma MMP-9 after 6 months of treatment compared with 47{\%} at baseline (P < .05). Conclusion: Prolonged administration of doxycycline is safe and well tolerated by patients with small asymptomatic AAAs and is associated with a gradual reduction in plasma MMP-9 levels. Further studies are needed to evaluate the long-term effects of doxycycline on the rate and extent of aneurysm growth and the potential use of plasma MMP-9 levels as a biomarker of aneurysm disease progression.",
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T1 - Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms

T2 - Report of a prospective (Phase II) multicenter study

AU - Baxter, B. Timothy

AU - Pearce, William H.

AU - Waltke, Eugene A.

AU - Littooy, Fred N.

AU - Hallett, John W.

AU - Kent, K. Craig

AU - Upchurch, Gilbert R.

AU - Chaikof, Elliot L.

AU - Mills, Joseph L

AU - Fleckten, Beverly

AU - Longo, G. Matt

AU - Lee, Jason K.

AU - Thompson, Robert W.

PY - 2002/7

Y1 - 2002/7

N2 - Background: The primary purpose of this study was to evaluate compliance, side effects, and safety associated with prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms (AAAs). A secondary goal was to determine how treatment with doxycycline influences circulating levels of matrix metalloproteinase-9 (MMP-9) in this patient population. Methods: Thirty-six patients with AAAs (30 men and 6 women; mean age, 69 ± 1 years) were enrolled into a 6-month phase II study to evaluate treatment with doxycycline (100 mg orally twice a day). Aneurysm size was measured before and after treatment, and compliance and side effects were monitored. Plasma levels of doxycycline were measured midway through the study, and plasma MMP-9 concentrations were measured at baseline, 3 months, and 6 months. Results: Thirty-three of the 36 patients (92%) completed 6 months of doxycycline treatment. Significant treatment-related side effects occurred in five patients (13.9%), including three with cutaneous photosensitivity reactions (8.3%), one with tooth discoloration (2.8%), and one with yeast infection (2.8%). A high rate of compliance with treatment was seen, despite minor but frequent side effects, including nonspecific gastrointestinal symptoms (25%), easily managed episodes of photosensitivity (22.2%), and reversible tooth discoloration (5.5%). The mean plasma doxycycline level after 3 months was 4.62 ± 0.68 ug/mL (median, 3.64 μg/mL; range, 1.31 to 14.39 μg/mL; n = 23 patients). No significant change was seen in AAA diameter (42.7 ± 1.3 mm at 6 months versus 41.0 ± 0.9 mm at baseline), and the overall rate of AAA expansion was 0.63% ± 0.25% per month. The mean plasma MMP-9 level (n = 19 patients) was elevated at baseline (118.9 ± 37.9 ng/mL; upper limit of normal, 85 ng/mL) but subsequently decreased to 83.8 ± 32.9 ng/mL at 3 months (not signifcant versus baseline) and to 66.4 ± 24.2 ng/mL at 6 months (P = .022 versus baseline). Only 21% of patients had an elevated level of plasma MMP-9 after 6 months of treatment compared with 47% at baseline (P < .05). Conclusion: Prolonged administration of doxycycline is safe and well tolerated by patients with small asymptomatic AAAs and is associated with a gradual reduction in plasma MMP-9 levels. Further studies are needed to evaluate the long-term effects of doxycycline on the rate and extent of aneurysm growth and the potential use of plasma MMP-9 levels as a biomarker of aneurysm disease progression.

AB - Background: The primary purpose of this study was to evaluate compliance, side effects, and safety associated with prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms (AAAs). A secondary goal was to determine how treatment with doxycycline influences circulating levels of matrix metalloproteinase-9 (MMP-9) in this patient population. Methods: Thirty-six patients with AAAs (30 men and 6 women; mean age, 69 ± 1 years) were enrolled into a 6-month phase II study to evaluate treatment with doxycycline (100 mg orally twice a day). Aneurysm size was measured before and after treatment, and compliance and side effects were monitored. Plasma levels of doxycycline were measured midway through the study, and plasma MMP-9 concentrations were measured at baseline, 3 months, and 6 months. Results: Thirty-three of the 36 patients (92%) completed 6 months of doxycycline treatment. Significant treatment-related side effects occurred in five patients (13.9%), including three with cutaneous photosensitivity reactions (8.3%), one with tooth discoloration (2.8%), and one with yeast infection (2.8%). A high rate of compliance with treatment was seen, despite minor but frequent side effects, including nonspecific gastrointestinal symptoms (25%), easily managed episodes of photosensitivity (22.2%), and reversible tooth discoloration (5.5%). The mean plasma doxycycline level after 3 months was 4.62 ± 0.68 ug/mL (median, 3.64 μg/mL; range, 1.31 to 14.39 μg/mL; n = 23 patients). No significant change was seen in AAA diameter (42.7 ± 1.3 mm at 6 months versus 41.0 ± 0.9 mm at baseline), and the overall rate of AAA expansion was 0.63% ± 0.25% per month. The mean plasma MMP-9 level (n = 19 patients) was elevated at baseline (118.9 ± 37.9 ng/mL; upper limit of normal, 85 ng/mL) but subsequently decreased to 83.8 ± 32.9 ng/mL at 3 months (not signifcant versus baseline) and to 66.4 ± 24.2 ng/mL at 6 months (P = .022 versus baseline). Only 21% of patients had an elevated level of plasma MMP-9 after 6 months of treatment compared with 47% at baseline (P < .05). Conclusion: Prolonged administration of doxycycline is safe and well tolerated by patients with small asymptomatic AAAs and is associated with a gradual reduction in plasma MMP-9 levels. Further studies are needed to evaluate the long-term effects of doxycycline on the rate and extent of aneurysm growth and the potential use of plasma MMP-9 levels as a biomarker of aneurysm disease progression.

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