<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02980003</url>
  </required_header>
  <id_info>
    <org_study_id>TEATE study</org_study_id>
    <nct_id>NCT02980003</nct_id>
  </id_info>
  <brief_title>PrevenTion of Contrast-inducEd nephroAThy With urinE Alkalinization</brief_title>
  <acronym>TEATE</acronym>
  <official_title>PrevenTion of Contrast-inducEd nephroAThy With urinE Alkalinization: the TEATE Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>G. d'Annunzio University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>G. d'Annunzio University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Intravascular administration of iodinated contrast media is an essential tool for&#xD;
      cardiovascular imaging and percutaneous coronary interventions. Nonetheless, the increasing&#xD;
      incidence of contrast-induced nephropathy (CIN) has become an important and prognostically&#xD;
      relevant problem along with the spreading of diagnostic and interventional procedures. CIN is&#xD;
      largely dependent on oxidative damage and represents a considerable cause of renal failure,&#xD;
      being associated with prolonged hospitalization and significant morbidity/mortality. The most&#xD;
      effective treatment strategy of this serious complication remains prevention, and several&#xD;
      preventive measures have been extensively investigated in the last few years. Pre-procedural&#xD;
      hydration is the best known and mostly accepted strategy. The administration of sodium&#xD;
      bicarbonate (HCO3) has controversial effects, and is likely to be ineffective when the&#xD;
      infused dose is unable to achieve adequate urine alkalinization. Since alkaline pH suppresses&#xD;
      the production of free radicals, increasing urine pH would be an attractive goal for CIN&#xD;
      prevention. In a randomized clinical trial the investigators will test the hypothesis that&#xD;
      urine alkalinization with either oral or i.v. bicarbonate on top of hydration alone is the&#xD;
      main determinant of CIN prevention in a population of patients with moderate or severe&#xD;
      chronic kidney disease scheduled for coronary angiography and/or angioplasty. If the&#xD;
      investigators, demonstrate non-significant differences in urine alkalinization (primary&#xD;
      endpoint) and incidence of CIN (secondary endpoint) between the bicarbonate groups, a&#xD;
      practical implication will be that oral administration is preferable for practical reasons&#xD;
      over the administration of i.v. bicarbonate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Contrast medium-induced nephropathy (CIN) is a recognized complication in coronary diagnostic&#xD;
      and interventional procedures, and is associated with prolonged hospitalization and adverse&#xD;
      clinical outcomes. The frequency of CIN ranges from 2% in low-risk patients to 50% in&#xD;
      high-risk patients. The most important risk factors for CIN development are pre-existing&#xD;
      renal failure, diabetes, age, volume and type of contrast medium. There are two main&#xD;
      pathogenetic mechanisms postulated to cause CIN:&#xD;
&#xD;
        1. a direct toxic action of contrast medium on kidney tubule cells, causing a disruption of&#xD;
           mitochondrial function, the generation of reactive oxygen species, and subsequent cell&#xD;
           injury and apoptosis;&#xD;
&#xD;
        2. vasoconstriction, reducing the blood flow through the renal medulla and causing ischemia&#xD;
           with cell damage The treatment of CIN is exclusively supportive. Treatment is&#xD;
           particularly recommended in patients with chronic kidney disease (CKD - mild, moderate&#xD;
           or severe, according to estimated glomerular filtration rate - eGFR). Several approaches&#xD;
           have been tested in the prevention of CIN with variable success. Adequate hydration is&#xD;
           widely accepted as the best method for prevention of CIN, and is today the only strategy&#xD;
           generally accepted by international guidelines (class of recommendation I, level of&#xD;
           evidence A). The use of N-acetyl cysteine, recommended even in the recent past, is not&#xD;
           supported by a recent randomized trial14 and a meta-analysis. Hemodialysis and&#xD;
           hemofiltration may be effective in preventive CIN, but are reserved to high-risk&#xD;
           patients. Attempts at preventing CIN with various medications, such as furosemide,&#xD;
           vitamin C, statins and numerous other, have been largely unsuccessful. The efficacy of&#xD;
           bicarbonate in the prevention of CIN has been extensively tested; the rationale is here&#xD;
           that urine alkalinization suppresses the formation of free radicals. Actually, studies&#xD;
           on bicarbonate have been controversial, varying from beneficial to toxic effects; this&#xD;
           could bring into question the role of alkalinizing procedures in preventing CIN.&#xD;
           Nevertheless, favorable results of prevention protocols using bicarbonate have been&#xD;
           noted in studies also documenting a significant alkalinization of urines; while a&#xD;
           similar protocol did not prove to be effective when the dose of bicarbonate was&#xD;
           insufficient to such aim. Moreover, Markota et al., in a recent study on patients with&#xD;
           estimated eGFR &gt;15 mL/min/1.73 m2 and scheduled for coronary angiography, after&#xD;
           documenting that Na/K citrate significantly reduced the incidence of CIN when compared&#xD;
           with hydration alone, have shown that patients having a urine pH &lt;6 had a more than&#xD;
           ten-fold higher incidence of CIN compared with patients whose urine pH was &gt;6.28 These&#xD;
           results confirm the potential role of urine alkalinization in preventing CIN and place&#xD;
           the oral administration of alkalinizing drugs as an attractive method compared to the&#xD;
           more complex, and not always effective, i.v. infusion of bicarbonate. Finally, oral&#xD;
           doses of bicarbonate may be sufficient to alkalinize the urine and thus to prevent CIN.&#xD;
           In a study recently published, an oral dose of 4 g was sufficient to obtain, two hours&#xD;
           after administration, an adequate urinary alkalinization with a pH &gt;7 in all&#xD;
           participants without side effects. This value was maintained and even magnified nearly 8&#xD;
           hours after the last dose. Interestingly, the Authors observed an additive effect after&#xD;
           the second dose, showing a nondepleting urine pH, despite the reported short half-life&#xD;
           of sodium bicarbonate.&#xD;
&#xD;
      Against this background, the investigators will here test the hypothesis that both oral and&#xD;
      i.v. bicarbonate are adequate strategies for CIN prevention in patients after coronary&#xD;
      angiography. Comparing the incidence of CIN according to urine pH achieved immediately before&#xD;
      angiography, the investigators aim at demonstrating that urine alkalinization is the real&#xD;
      goal, and that results are here largely independent from the strategy adopted to achieve it.&#xD;
      The investigators will therefore compare the efficacy in alkalinizing urine and preventing&#xD;
      CIN of three different strategies: hydration alone; hydration plus i.v. sodium bicarbonate;&#xD;
      and hydration plus oral bicarbonate. Favorable results of the bicarbonate groups compared to&#xD;
      the control group could increase the evidence supporting the use of alkalinizing strategies&#xD;
      to prevent CIN; at the same time, non-inferiority results of the oral group compared to i.v.&#xD;
      bicarbonate group could suggest the more practical oral administration as the preferred&#xD;
      prevention strategy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2015</start_date>
  <completion_date type="Actual">May 1, 2021</completion_date>
  <primary_completion_date type="Actual">October 30, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The incidence of CIN according to urine alkalinization achieved immediately before angiography</measure>
    <time_frame>48 hours after randomization</time_frame>
    <description>The investigators primary hypothesis is that the incidence of CIN definition is significantly different in patients achieving urine alkalinization compared with patients not achieving it.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Urine PH</measure>
    <time_frame>48 hours after randomization</time_frame>
    <description>The investigators hypothesis is that the proportion of patients achieving urine alkalinization (pH &gt;6) will be greater in patients allocated to the sodium bicarbonate group or the oral sodium/potassium citrate group compared to the control group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the incidence of CIN in three treatment groups</measure>
    <time_frame>48 hours after coronary angiography</time_frame>
    <description>The investigators hypothesis is that the proportion of patients that develop a CIN will be greater in patients allocated to the control group compared to patients assigned to other groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>non-inferiority comparison between oral sodium bicarbonate group and i.v. sodium</measure>
    <time_frame>48 hours after coronary angiography</time_frame>
    <description>The non-inferiority of oral bicarbonate group respect to i.v. sodium bicarbonate group will be evaluated in term of incidence of CIN.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>non-inferiority comparison between oral sodium bicarbonate group and i.v. sodium bicarbonate</measure>
    <time_frame>48 hours after coronary angiography</time_frame>
    <description>the non-inferiority of oral bicarbonate group respect to i.v. sodium bicarbonate group will be evaluated in term of proportion of patients achieving urine alkalinization</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">240</enrollment>
  <condition>Acute Kidney Injury</condition>
  <condition>Contrast Media Reaction</condition>
  <arm_group>
    <arm_group_label>isotonic saline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients will start hydration with isotonic saline 6 hours before angiography and continue for 12 hours after the procedure. The infusion rate will be 1 mL/kg/h in the first 5 hours they will receive isotonic saline at 1 mL/kg/h (reduced to 0.5 mL/kg/h if with ejection fraction &lt;35% or New York Heart Association (NYHA) functional class III or IV). Then, will be infused at 3 mL/kg/h for 1 hour immediately before contrast medium injection; following this, patients will receive the same fluid at a rate of 1 mL/kg/h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>i.v. sodium bicarbonate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>in the first 5 hours patients will receive isotonic saline at 1 mL/kg/h (reduced to 0.5 mL/kg/h if with ejection fraction &lt;35% or NYHA functional class III or IV). Then, a solution of 1.4% sodium bicarbonate (167 mEq/L; 334 milliosmol (mOsm/L)) will be infused: the initial intravenous bolus will be 3 mL/kg/h for 1 hour immediately before contrast medium injection; following this, patients will receive the same fluid at a rate of 1 mL/kg/h (reduced to 0.5 mL/kg/h if with ejection fraction &lt;35% or NYHA functional class III or IV) during the exposure to contrast and for 6 hours after the procedure. Later, patients will resume hydration with isotonic saline for further 6 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>oral sodium bicarbonate:</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients will start hydration with isotonic saline as well as Arm Hydration Alone. One hour before the angiography and 3 hours after patients will receive oral sodium bicarbonate at the dose of 4 g (47.6 mEq) dissolved in 60 mL of water. The drug will be weighed with a precision balance with a sensitivity of ± 0.1 mg and placed in a labeled sterile plastic container. The label will report the lot number, expiry date of the sodium bicarbonate lot, the signature of the pharmacist carrying out the weighing process, a serial number to identify the sample and the patient identification number.&#xD;
Documentation will be stored in the Laboratory of Galenic Preparations, Pharmacy Division, of the hospital.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>isotonic saline</intervention_name>
    <description>patients will start hydration with isotonic saline 6 hours before angiography and continue for 12 hours after the procedure.</description>
    <arm_group_label>isotonic saline</arm_group_label>
    <other_name>Isotonic sodium chloride solution</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>i.v. sodium bicarbonate</intervention_name>
    <description>patients will start hydration with isotonic saline 6 hours before angiography and continue for 12 hours after the procedure. The patient receives solution of 1.4% sodium bicarbonate (167 mEq/L; 334 mOsm/L) one hours and six hours after procedure.</description>
    <arm_group_label>i.v. sodium bicarbonate</arm_group_label>
    <other_name>HCO3</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>oral sodium bicarbonate</intervention_name>
    <description>patients will start hydration with isotonic saline 6 hours before angiography and continue for 12 hours after the procedure. One hour before the angiography and 3 hours after patients will receive oral sodium bicarbonate at the dose of 4 g (47.6 mEq) dissolved in 60 mL of water</description>
    <arm_group_label>oral sodium bicarbonate:</arm_group_label>
    <other_name>HCO3</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Consecutive patients scheduled for coronary angiography and/or angioplasty;&#xD;
&#xD;
          -  eGFR &lt;60 mL/min/1.73 m2, but &gt;15 mL/min/1.73 m2 (MDRD formula).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  acute renal insufficiency;&#xD;
&#xD;
          -  emergency catheterization (e.g., STEMI patients) preventing the possibility of&#xD;
             pretreatments;&#xD;
&#xD;
          -  a history of adverse reactions to contrast media;&#xD;
&#xD;
          -  use of potentially nephrotoxic drugs (non-steroidal anti-inflammatory drugs,&#xD;
             aminoglycosides, sulphonamides, cyclosporin, tacrolimus, methotrexate or platinum&#xD;
             complexes) from 48 hours before to 24 hours after the procedure, but allowing drugs&#xD;
             deemed essential for cardiovascular therapy (diuretics, acetylsalicylic acid,&#xD;
             angiotensinconverting enzyme inhibitors, angiotensin receptor blockers or aliskiren);&#xD;
&#xD;
          -  pulmonary edema;&#xD;
&#xD;
          -  multiple myeloma and other monoclonal gammopathies;&#xD;
&#xD;
          -  factors predisposing to kidney injury: diarrhea, vomiting, dehydration or bleeding;&#xD;
&#xD;
          -  exposure to contrast media within 7 days before the procedure; pregnancy; -&#xD;
&#xD;
          -  hypersensitivity to the active substance or to any of the excipients;&#xD;
&#xD;
          -  Metabolic or respiratory alkalosis, particularly if hypochloremic (vomiting,&#xD;
             gastrointestinal losses, diuretic therapy);&#xD;
&#xD;
          -  Hypocalcemia;&#xD;
&#xD;
          -  use of N-acetyl cysteine, theophylline, dopamine, fenoldopam, mannitol, citrate or&#xD;
             bicarbonate within 48 hours before coronary angiography;&#xD;
&#xD;
          -  Chronic and / or acute therapy with corticosteroid, quinidine, ephedrine and&#xD;
             pseudoephedrine;&#xD;
&#xD;
          -  urinary tract infections.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Raffaele De Caterina</last_name>
    <role>Principal Investigator</role>
    <affiliation>G. d'Annunzio University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institute of Cardiology - Center of Excellence on Aging, G. d'Annunzio University</name>
      <address>
        <city>Chieti</city>
        <state>CH</state>
        <zip>66100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <results_reference>
    <citation>Parfrey PS, Griffiths SM, Barrett BJ, Paul MD, Genge M, Withers J, Farid N, McManamon PJ. Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study. N Engl J Med. 1989 Jan 19;320(3):143-9. doi: 10.1056/NEJM198901193200303.</citation>
    <PMID>2643041</PMID>
  </results_reference>
  <results_reference>
    <citation>Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, Bersin RM, Van Moore A, Simonton CA 3rd, Rittase RA, Norton HJ, Kennedy TP. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004 May 19;291(19):2328-34. doi: 10.1001/jama.291.19.2328.</citation>
    <PMID>15150204</PMID>
  </results_reference>
  <results_reference>
    <citation>Markota D, Markota I, Starcevic B, Tomic M, Prskalo Z, Brizic I. Prevention of contrast-induced nephropathy with Na/K citrate. Eur Heart J. 2013 Aug;34(30):2362-7. doi: 10.1093/eurheartj/eht009. Epub 2013 Jan 24.</citation>
    <PMID>23349296</PMID>
  </results_reference>
  <results_reference>
    <citation>Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW, Mathew V, Garratt KN, Holmes DR Jr. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 2002 May 14;105(19):2259-64. doi: 10.1161/01.cir.0000016043.87291.33.</citation>
    <PMID>12010907</PMID>
  </results_reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>November 5, 2016</study_first_submitted>
  <study_first_submitted_qc>November 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 2, 2016</study_first_posted>
  <last_update_submitted>May 19, 2022</last_update_submitted>
  <last_update_submitted_qc>May 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>G. d'Annunzio University</investigator_affiliation>
    <investigator_full_name>Raffaele De Caterina</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>contrast media</keyword>
  <keyword>contrast-induced acute kidney injury (AKI)</keyword>
  <keyword>contrast-induced nephropathy (CIN)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Kidney Injury</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02980003
org study id: TEATE study
nct id: NCT02980003
lead sponsor: 
has dmc: Yes
Intravascular administration of iodinated contrast media is an essential tool for
      cardiovascular imaging and percutaneous coronary interventions. Nonetheless, the increasing
      incidence of contrast-induced nephropathy (CIN) has become an important and prognostically
      relevant problem along with the spreading of diagnostic and interventional procedures. CIN is
      largely dependent on oxidative damage and represents a considerable cause of renal failure,
      being associated with prolonged hospitalization and significant morbidity/mortality. The most
      effective treatment strategy of this serious complication remains prevention, and several
      preventive measures have been extensively investigated in the last few years. Pre-procedural
      hydration is the best known and mostly accepted strategy. The administration of sodium
      bicarbonate (HCO3) has controversial effects, and is likely to be ineffective when the
      infused dose is unable to achieve adequate urine alkalinization. Since alkaline pH suppresses
      the production of free radicals, increasing urine pH would be an attractive goal for CIN
      prevention. In a randomized clinical trial the investigators will test the hypothesis that
      urine alkalinization with either oral or i.v. bicarbonate on top of hydration alone is the
      main determinant of CIN prevention in a population of patients with moderate or severe
      chronic kidney disease scheduled for coronary angiography and/or angioplasty. If the
      investigators, demonstrate non-significant differences in urine alkalinization (primary
      endpoint) and incidence of CIN (secondary endpoint) between the bicarbonate groups, a
      practical implication will be that oral administration is preferable for practical reasons
      over the administration of i.v. bicarbonate.
Contrast medium-induced nephropathy (CIN) is a recognized complication in coronary diagnostic
      and interventional procedures, and is associated with prolonged hospitalization and adverse
      clinical outcomes. The frequency of CIN ranges from 2% in low-risk patients to 50% in
      high-risk patients. The most important risk factors for CIN development are pre-existing
      renal failure, diabetes, age, volume and type of contrast medium. There are two main
      pathogenetic mechanisms postulated to cause CIN:

        1. a direct toxic action of contrast medium on kidney tubule cells, causing a disruption of
           mitochondrial function, the generation of reactive oxygen species, and subsequent cell
           injury and apoptosis;

        2. vasoconstriction, reducing the blood flow through the renal medulla and causing ischemia
           with cell damage The treatment of CIN is exclusively supportive. Treatment is
           particularly recommended in patients with chronic kidney disease (CKD - mild, moderate
           or severe, according to estimated glomerular filtration rate - eGFR). Several approaches
           have been tested in the prevention of CIN with variable success. Adequate hydration is
           widely accepted as the best method for prevention of CIN, and is today the only strategy
           generally accepted by international guidelines (class of recommendation I, level of
           evidence A). The use of N-acetyl cysteine, recommended even in the recent past, is not
           supported by a recent randomized trial14 and a meta-analysis. Hemodialysis and
           hemofiltration may be effective in preventive CIN, but are reserved to high-risk
           patients. Attempts at preventing CIN with various medications, such as furosemide,
           vitamin C, statins and numerous other, have been largely unsuccessful. The efficacy of
           bicarbonate in the prevention of CIN has been extensively tested; the rationale is here
           that urine alkalinization suppresses the formation of free radicals. Actually, studies
           on bicarbonate have been controversial, varying from beneficial to toxic effects; this
           could bring into question the role of alkalinizing procedures in preventing CIN.
           Nevertheless, favorable results of prevention protocols using bicarbonate have been
           noted in studies also documenting a significant alkalinization of urines; while a
           similar protocol did not prove to be effective when the dose of bicarbonate was
           insufficient to such aim. Moreover, Markota et al., in a recent study on patients with
           estimated eGFR >15 mL/min/1.73 m2 and scheduled for coronary angiography, after
           documenting that Na/K citrate significantly reduced the incidence of CIN when compared
           with hydration alone, have shown that patients having a urine pH <6 had a more than
           ten-fold higher incidence of CIN compared with patients whose urine pH was >6.28 These
           results confirm the potential role of urine alkalinization in preventing CIN and place
           the oral administration of alkalinizing drugs as an attractive method compared to the
           more complex, and not always effective, i.v. infusion of bicarbonate. Finally, oral
           doses of bicarbonate may be sufficient to alkalinize the urine and thus to prevent CIN.
           In a study recently published, an oral dose of 4 g was sufficient to obtain, two hours
           after administration, an adequate urinary alkalinization with a pH >7 in all
           participants without side effects. This value was maintained and even magnified nearly 8
           hours after the last dose. Interestingly, the Authors observed an additive effect after
           the second dose, showing a nondepleting urine pH, despite the reported short half-life
           of sodium bicarbonate.

      Against this background, the investigators will here test the hypothesis that both oral and
      i.v. bicarbonate are adequate strategies for CIN prevention in patients after coronary
      angiography. Comparing the incidence of CIN according to urine pH achieved immediately before
      angiography, the investigators aim at demonstrating that urine alkalinization is the real
      goal, and that results are here largely independent from the strategy adopted to achieve it.
      The investigators will therefore compare the efficacy in alkalinizing urine and preventing
      CIN of three different strategies: hydration alone; hydration plus i.v. sodium bicarbonate;
      and hydration plus oral bicarbonate. Favorable results of the bicarbonate groups compared to
      the control group could increase the evidence supporting the use of alkalinizing strategies
      to prevent CIN; at the same time, non-inferiority results of the oral group compared to i.v.
      bicarbonate group could suggest the more practical oral administration as the preferred
      prevention strategy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: The incidence of CIN according to urine alkalinization achieved immediately before angiography
time frame: 48 hours after randomization
description: The investigators primary hypothesis is that the incidence of CIN definition is significantly different in patients achieving urine alkalinization compared with patients not achieving it.
measure: Urine PH
time frame: 48 hours after randomization
description: The investigators hypothesis is that the proportion of patients achieving urine alkalinization (pH >6) will be greater in patients allocated to the sodium bicarbonate group or the oral sodium/potassium citrate group compared to the control group
measure: the incidence of CIN in three treatment groups
time frame: 48 hours after coronary angiography
description: The investigators hypothesis is that the proportion of patients that develop a CIN will be greater in patients allocated to the control group compared to patients assigned to other groups
measure: non-inferiority comparison between oral sodium bicarbonate group and i.v. sodium
time frame: 48 hours after coronary angiography
description: The non-inferiority of oral bicarbonate group respect to i.v. sodium bicarbonate group will be evaluated in term of incidence of CIN.
measure: non-inferiority comparison between oral sodium bicarbonate group and i.v. sodium bicarbonate
time frame: 48 hours after coronary angiography
description: the non-inferiority of oral bicarbonate group respect to i.v. sodium bicarbonate group will be evaluated in term of proportion of patients achieving urine alkalinization
arm group label: isotonic saline
arm group type: Active Comparator
description: patients will start hydration with isotonic saline 6 hours before angiography and continue for 12 hours after the procedure. The infusion rate will be 1 mL/kg/h in the first 5 hours they will receive isotonic saline at 1 mL/kg/h (reduced to 0.5 mL/kg/h if with ejection fraction <35% or New York Heart Association (NYHA) functional class III or IV). Then, will be infused at 3 mL/kg/h for 1 hour immediately before contrast medium injection; following this, patients will receive the same fluid at a rate of 1 mL/kg/h
arm group label: i.v. sodium bicarbonate
arm group type: Active Comparator
description: in the first 5 hours patients will receive isotonic saline at 1 mL/kg/h (reduced to 0.5 mL/kg/h if with ejection fraction <35% or NYHA functional class III or IV). Then, a solution of 1.4% sodium bicarbonate (167 mEq/L; 334 milliosmol (mOsm/L)) will be infused: the initial intravenous bolus will be 3 mL/kg/h for 1 hour immediately before contrast medium injection; following this, patients will receive the same fluid at a rate of 1 mL/kg/h (reduced to 0.5 mL/kg/h if with ejection fraction <35% or NYHA functional class III or IV) during the exposure to contrast and for 6 hours after the procedure. Later, patients will resume hydration with isotonic saline for further 6 hours.
arm group label: oral sodium bicarbonate:
arm group type: Experimental
description: patients will start hydration with isotonic saline as well as Arm Hydration Alone. One hour before the angiography and 3 hours after patients will receive oral sodium bicarbonate at the dose of 4 g (47.6 mEq) dissolved in 60 mL of water. The drug will be weighed with a precision balance with a sensitivity of ± 0.1 mg and placed in a labeled sterile plastic container. The label will report the lot number, expiry date of the sodium bicarbonate lot, the signature of the pharmacist carrying out the weighing process, a serial number to identify the sample and the patient identification number.
Documentation will be stored in the Laboratory of Galenic Preparations, Pharmacy Division, of the hospital.
intervention type: Drug
intervention name: isotonic saline
description: patients will start hydration with isotonic saline 6 hours before angiography and continue for 12 hours after the procedure.
arm group label: isotonic saline
other name: Isotonic sodium chloride solution
intervention type: Drug
intervention name: i.v. sodium bicarbonate
description: patients will start hydration with isotonic saline 6 hours before angiography and continue for 12 hours after the procedure. The patient receives solution of 1.4% sodium bicarbonate (167 mEq/L; 334 mOsm/L) one hours and six hours after procedure.
arm group label: i.v. sodium bicarbonate
other name: HCO3
intervention type: Drug
intervention name: oral sodium bicarbonate
description: patients will start hydration with isotonic saline 6 hours before angiography and continue for 12 hours after the procedure. One hour before the angiography and 3 hours after patients will receive oral sodium bicarbonate at the dose of 4 g (47.6 mEq) dissolved in 60 mL of water
arm group label: oral sodium bicarbonate:
other name: HCO3
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Raffaele De Caterina
role: Principal Investigator
affiliation: G. d'Annunzio University
facility: 
country: Italy
citation: Parfrey PS, Griffiths SM, Barrett BJ, Paul MD, Genge M, Withers J, Farid N, McManamon PJ. Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study. N Engl J Med. 1989 Jan 19;320(3):143-9. doi: 10.1056/NEJM198901193200303.
PMID: 2643041
citation: Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, Bersin RM, Van Moore A, Simonton CA 3rd, Rittase RA, Norton HJ, Kennedy TP. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004 May 19;291(19):2328-34. doi: 10.1001/jama.291.19.2328.
PMID: 15150204
citation: Markota D, Markota I, Starcevic B, Tomic M, Prskalo Z, Brizic I. Prevention of contrast-induced nephropathy with Na/K citrate. Eur Heart J. 2013 Aug;34(30):2362-7. doi: 10.1093/eurheartj/eht009. Epub 2013 Jan 24.
PMID: 23349296
citation: Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW, Mathew V, Garratt KN, Holmes DR Jr. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 2002 May 14;105(19):2259-64. doi: 10.1161/01.cir.0000016043.87291.33.
PMID: 12010907
responsible party type: Principal Investigator
investigator affiliation: G. d'Annunzio University
investigator full name: Raffaele De Caterina
investigator title: Principal Investigator
mesh term: Acute Kidney Injury
sharing ipd: No