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

Bernard 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 Matthew 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

  • Surgery
  • Cardiology and Cardiovascular Medicine

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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, Bernard 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 Matthew; 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, Bernard 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 Matthew ; 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.",
author = "Baxter, {Bernard Timothy} and Pearce, {William H.} and Waltke, {Eugene A.} and Littooy, {Fred N.} and Hallett, {John W.} and Kent, {K. Craig} and Upchurch, {Gilbert R.} and Chaikof, {Elliot L.} and Mills, {Joseph L.} and Beverly Fleckten and Longo, {G Matthew} and Lee, {Jason K.} and Thompson, {Robert W.}",
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language = "English (US)",
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TY - JOUR

T1 - Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms

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

AU - Baxter, Bernard 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 Matthew

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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