Clinical Investigations: AHJ Online ExclusiveEffects of the thromboxane synthetase inhibitor and receptor antagonist terbogrel in patients with primary pulmonary hypertension*,**,★
Section snippets
Study design
The study was approved by the Institutional Research Ethics Review Boards of each participating institution. It used a multicenter, randomized, double-blind, placebo-controlled protocol structured to evaluate the safety and efficacy of 12 weeks of oral terbogrel therapy in 135 patients with New York Heart Association (NYHA) functional classification II and III PPH, at doses of 0 mg twice a day (bid; placebo), 100 mg bid, or 200 mg bid (45 patients per group). The primary efficacy endpoint was
Study termination and patient enrollment
The Data Safety Monitoring Board performed an interim analysis after approximately one third of the patients had completed the trial. They recommended stopping enrollment on the basis of the incidence of the significant side effect of leg pain. They also recommended that an analysis be conducted to explore the efficacy of terbogrel to determine whether to continue the study or terminate it prematurely. This analysis was conducted by the Steering Committee, which recommended premature
Discussion
With examination from an intention-to-treat perspective, with all enrolled patients included, terbogrel was ineffective as a therapeutic agent in PPH. However, the primary endpoint was a change in 6-minute walk distance, and this endpoint was greatly confounded by the unanticipated problem of leg pain. Moreover, many of the patients who remained in the study for the entire 12 weeks had at least temporarily reduced or interrupted their terbogrel intake at some time because of leg pain. This may
Acknowledgements
We thank Patricia Price and Terri Hagan for assistance with the prostaglandin assays. David Langleben, MD, is a Chercheur Boursier Clinicien (Research Scholar) of the Fonds de la Recherche en Sante du Quebec.
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Cited by (0)
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Conflict of interest: Drs Langleben, Christman, Barst, Galie, Higgenbottam, Kneussl, Naeije, Simonneau, Rich, Robbins, Oudiz, McGoon, Badesch, Levy, Mehta, Seeger, and Soler were principal investigators or members of the Steering Committee of the study and, as such, received indirect support from Boehringer Ingelheim, Inc. Drs Dias and Riedel and Mr Korducki are employees of Boehringer Ingelheim, Inc.
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Reprint requests: D. Langleben, MD, Jewish General Hospital, 3755 Cote Ste, Catherine, Montreal, Quebec, Canada H3T 1E2.
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E-mail: [email protected]