title: Evaluation of the relationship between effervescent paracetamol and blood pressure: clinical trial.
abstract: BACKGROUND
  Paracetamol's solubility is achieved by adding to the excipient sodium salts, either as bicarbonate, carbonate or citrate. As the relationship between salt and hypertension is well known, due to the sodium content it has raised a hypothesis that may interfere with the control of that risk factor. Therefore, the objective of this study is to evaluate the effect on blood pressure of effervescent paracetamol compared to non-effervescent, in hypertensive patients.
  
  
  METHODS
  This is the protocol of a phase IV multicenter clinical trial, randomized, controlled, crossover, open, which will compare the effect of two different formulations of paracetamol (effervescent or non-effervescent) in the blood pressure of hypertensive patients, with a seven weeks follow up. 49 controlled hypertensive patients will be included (clinical BP lower than 150 and 95 mmHg, and lower than 135 mmHg and 85 mmHg in patients with diabetes or a history of cardiovascular event, and daytime ambulatory measurements lower than 140 and 90 mmHg) and mild to moderate pain (Visual Analog Scale between 1 and 4). The study was approved by the ethics committee of the Fundació Jordi Gol i Gurina and following standards of good clinical practice. The primary endpoint will be the variations in systolic BP in 24 h Ambulatory Blood Pressure Monitoring, considering significant differences 2 or more mmHg among those treated with non-effervescent and effervescent formulations. Intention-to-treat and per-protocol analysis will be held.
  
  
  CONCLUSIONS
  Despite the broad recommendation not to use effervescent drugs in patients with hypertension, there are relatively little studies that show exactly this pressor effect due to sodium in salt that gives the effervescence of the product. This is the first clinical trial designed to study the effect of effervescence compared to the non-effervescent, in well-controlled hypertensive patients with mild to moderate pain, performed in routine clinical practice.
  
  
  BACKGROUND
  NCT 02514538.
authors.affiliation: CAP Gòtic, Institut Català de la Salut, Barcelona, Spain. alexpben2010@gmail.com.
authors.forename: Mencia
authors.initials: M
authors.lastname: Benitez-Camps
authors.affiliation: CAP La Mina, Institut Català de la Salut, Barcelona, Spain. 23561evb@comb.cat.|Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Barcelona, Spain. 23561evb@comb.cat.
authors.forename: Ernest
authors.initials: E
authors.lastname: Vinyoles-Bargalló
authors.affiliation: CAP Gòtic, Institut Català de la Salut, Barcelona, Spain. oriolreba@gmail.com.
authors.forename: Oriol
authors.initials: O
authors.lastname: Rebagliato-Nadal
authors.affiliation: Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Barcelona, Spain. rmorros@idiapjgol.org.|Departament de farmacologia i terapèutica Universitat Autònoma de Barcelona, Barcelona, Spain. rmorros@idiapjgol.org.
authors.forename: Rosa
authors.initials: R
authors.lastname: Morros-Pedrós
authors.affiliation: Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Barcelona, Spain. hpera@idiapjgol.org.
authors.forename: Helena
authors.initials: H
authors.lastname: Pera-Pujadas
authors.affiliation: CAP Gòtic, Institut Català de la Salut, Barcelona, Spain. 932324800@telefonica.net.
authors.forename: Antoni
authors.initials: A
authors.lastname: Dalfó-Baqué
authors.affiliation: CAP Santa Coloma de Gramenet, Institut Català de la Salut, Barcelona, Spain. ilopezp.bnm.ics@gencat.cat.
authors.forename: Ignacio
authors.initials: I
authors.lastname: López-Pavón
authors.affiliation: CAP Santa Coloma de Gramenet, Institut Català de la Salut, Barcelona, Spain. croca.ics@gencat.cat.
authors.forename: Carlos
authors.initials: C
authors.lastname: Roca-Sánchez
authors.affiliation: CAP El Maresme, Institut Català de la Salut, Barcelona, Spain. rosamcoma@gmail.com.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Coma-Carbó
authors.affiliation: CAP Sardenya, Barcelona, Spain. 14733mfw@comb.cat.
authors.forename: Mariano
authors.initials: M
authors.lastname: De La Figuera Von Wichmann
authors.affiliation: CAP Badia, Institut Català de la Salut, Badia del Vallès, Barcelona, Spain. lucasmengual@comb.cat.
authors.forename: Lucas
authors.initials: L
authors.lastname: Mengual-Martínez
authors.affiliation: CAP Badia, Institut Català de la Salut, Badia del Vallès, Barcelona, Spain. mcyuste.mn.ics@gencat.cat.
authors.forename: Carmen
authors.initials: C
authors.lastname: Yuste-Marco
authors.affiliation: CAP Badia, Institut Català de la Salut, Badia del Vallès, Barcelona, Spain. mteixido.mn.ics@gencat.cat.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Teixidó-Colet
authors.affiliation: CAP Baix Ebre, Institut Català de la Salut, Tarragona, Spain. jmpepio.ebre.ics@gencat.cat.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Pepió i Vilaubí
authors.affiliation: CAP Baix Ebre, Institut Català de la Salut, Tarragona, Spain. rciurana.ebre.ics@gencat.cat.
authors.forename: Riera
authors.initials: R
authors.lastname: Ciurana-Tost
authors.affiliation: CAP Gòtic, Institut Català de la Salut, Barcelona, Spain. 16608mpv@comb.cat.
authors.forename: Rosa
authors.initials: R
authors.lastname: Pou-Vila
authors.affiliation: CAP Gòtic, Institut Català de la Salut, Barcelona, Spain. mavilacoll@gmail.com.
authors.forename: Ma Antònia
authors.initials: MA
authors.lastname: Vila-Coll
authors.affiliation: CAP Gòtic, Institut Català de la Salut, Barcelona, Spain. jmbordas.bcn.ics@gencat.cat.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Bordas-Julve
authors.affiliation: CAP Gòtic, Institut Català de la Salut, Barcelona, Spain. raragonesf.bcn.ics@gencat.cat.
authors.forename: Rosa
authors.initials: R
authors.lastname: Aragonès-Forès
authors.affiliation: CAP Gòtic, Institut Català de la Salut, Barcelona, Spain. fjpr1985@hotmail.com.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Pelegrina-Rodríguez
authors.affiliation: CAP La Mina, Institut Català de la Salut, Barcelona, Spain. jagudo.bcn.ics@gencat.cat.
authors.forename: Josep
authors.initials: J
authors.lastname: Agudo-Ugena
authors.affiliation: CS Mina del Morro, País Vasco, Spain. carlos.blancomata@osakidetza.net.
authors.forename: Carlos
authors.initials: C
authors.lastname: Blanco-Mata
authors.affiliation: CS Bolueta, País Vasco, Spain. jonjoseba.delaiglesiaberrojalbiz@osakidetza.net.
authors.forename: Jon
authors.initials: J
authors.lastname: de la Iglesia Berrojalbiz
authors.affiliation: Clinical Trial Monitoring, Pais Vasco, Spain. natalia.burgosalonso@osakidetza.net.
authors.forename: Natalia
authors.initials: N
authors.lastname: Burgos-Alonso
authors.affiliation: Clinical Trial Monitoring and Coordination, País Vasco, Spain. macruz.gomezfernandez@osakidetza.net.
authors.forename: Maria Cruz
authors.initials: MC
authors.lastname: Gómez-Fernández
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D002245:Carbon Dioxide / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002985:Clinical Protocols; D018592:Cross-Over Studies; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D057194:Intention to Treat Analysis; D019338:Polypharmacy; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D012995:Solubility; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D000959:Antihypertensive Agents; D002245:Carbon Dioxide; D000082:Acetaminophen