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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02476253
Other study ID # 9260
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date May 5, 2015
Est. completion date May 29, 2017

Study information

Verified date June 2017
Source University Hospital, Montpellier
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of the present study is to compare the adjunct treatment of metabolic or mixed severe acidosis in the critically ill using Sodium Bicarbonate as a buffer to increase the plasma pH vs no buffering therapy. The study is a randomized multiple center clinical trial with the outcome as a primary endpoint.


Description:

- Design: randomized multiple center clinical trial, open label - Arms: intravenous 4.2% Sodium Bicarbonate vs no additional treatment - Inclusion: age of 18 yo or above, critically ill patient with a SOFA score of 4 or above, lactatemia of 2mmol/l or above, with pH of 7.20 or below and PaCO2 of 45mmHg or below and bicarbonatemia of 20mmol/l or below - Exclusion: single respiratory disorder (PaCO2 > 50 mmHg, Bicarbonatemia equal or higher than (PaCO2-40)/10 + 24 ; acute diarrhea, ileostomy or biliary drainage ; stage IV kidney failure or chronic dialysis ; tubular acidosis, ketoacidosis, high anion gap acids poisoning (PEG, aspirin, methanol) ; PaCO2 equal to 45mmHg or above and spontaneous breathing, pregnancy, protected patients, moribund patient (life expectancy of 48h or below) - Randomization: website randomization with stratification on age, presence of sepsis at inclusion, renal failure - Intervention: experimental arm: intravenous 4.2% Sodium Bicarbonate 125 to 250ml in 30min up to 1000ml/24h. The target is a plasma pH of 7.30 or above. - An interim statistical analysis is planned when 200 patients will be included


Recruitment information / eligibility

Status Completed
Enrollment 400
Est. completion date May 29, 2017
Est. primary completion date May 29, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Age of 18 yo or above, - Critically ill patient with a SOFA score of 4 or above, - Lactatemia of 2mmol/l or above, with pH of 7.20 or below and PaCO2 of 45mmHg or below and bicarbonatemia of 20mmol/l or below Exclusion Criteria: - Administration of Sodium Bicarbonate 24 hours before inclusion - Single respiratory disorder (PaCO2 > 50 mmHg, Bicarbonatemia equal or higher than (PaCO2-40)/10 + 24 - Acute diarrhea, ileostomy or biliary drainage - Stage IV kidney failure or chronic dialysis - Tubular acidosis, ketoacidosis, high anion gap acids poisoning (PEG, aspirin, methanol) - PaCO2 equal to 45mmHg or above and spontaneous breathing, pregnancy, protected patients, moribund patient (life expectancy of 48h or below)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Sodium Bicarbonate
Intravenous 4.2% Sodium Bicarbonate 125ml to 250ml / 30min up to 1000ml/24h to maintain plasma pH equal or greater than 7.30

Locations

Country Name City State
France DAR St Eloi Montpellier

Sponsors (1)

Lead Sponsor Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

References & Publications (38)

American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005 Feb 15;171(4):388-416. doi: 10.1164/rccm.200405-644ST. No abstract available. — View Citation

Bersin RM, Chatterjee K, Arieff AI. Metabolic and hemodynamic consequences of sodium bicarbonate administration in patients with heart disease. Am J Med. 1989 Jul;87(1):7-14. doi: 10.1016/s0002-9343(89)80476-0. — View Citation

Brar SS, Shen AY, Jorgensen MB, Kotlewski A, Aharonian VJ, Desai N, Ree M, Shah AI, Burchette RJ. Sodium bicarbonate vs sodium chloride for the prevention of contrast medium-induced nephropathy in patients undergoing coronary angiography: a randomized trial. JAMA. 2008 Sep 3;300(9):1038-46. doi: 10.1001/jama.300.9.1038. — View Citation

Brochard L, Abroug F, Brenner M, Broccard AF, Danner RL, Ferrer M, Laghi F, Magder S, Papazian L, Pelosi P, Polderman KH; ATS/ERS/ESICM/SCCM/SRLF Ad Hoc Committee on Acute Renal Failure. An Official ATS/ERS/ESICM/SCCM/SRLF Statement: Prevention and Management of Acute Renal Failure in the ICU Patient: an international consensus conference in intensive care medicine. Am J Respir Crit Care Med. 2010 May 15;181(10):1128-55. doi: 10.1164/rccm.200711-1664ST. — View Citation

Cohen MV, Yang XM, Downey JM. The pH hypothesis of postconditioning: staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis. Circulation. 2007 Apr 10;115(14):1895-903. doi: 10.1161/CIRCULATIONAHA.106.675710. Epub 2007 Mar 26. — View Citation

Cooper DJ, Walley KR, Wiggs BR, Russell JA. Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study. Ann Intern Med. 1990 Apr 1;112(7):492-8. doi: 10.7326/0003-4819-112-7-492. — View Citation

Correction de l'acidose métabolique en réanimation. 1999 [cited; Available from: http://www.urgences-serveur.fr/IMG/pdf/correction_acidose.pdf

Dubin A, Menises MM, Masevicius FD, Moseinco MC, Kutscherauer DO, Ventrice E, Laffaire E, Estenssoro E. Comparison of three different methods of evaluation of metabolic acid-base disorders. Crit Care Med. 2007 May;35(5):1264-70. doi: 10.1097/01.CCM.0000259536.11943.90. — View Citation

El-Solh AA, Abou Jaoude P, Porhomayon J. Bicarbonate therapy in the treatment of septic shock: a second look. Intern Emerg Med. 2010 Aug;5(4):341-7. doi: 10.1007/s11739-010-0351-3. Epub 2010 Feb 19. Erratum In: Intern Emerg Med. 2010 Aug;5(4):367. — View Citation

Fang ZX, Li YF, Zhou XQ, Zhang Z, Zhang JS, Xia HM, Xing GP, Shu WP, Shen L, Yin GQ. Effects of resuscitation with crystalloid fluids on cardiac function in patients with severe sepsis. BMC Infect Dis. 2008 Apr 17;8:50. doi: 10.1186/1471-2334-8-50. — View Citation

Fencl V, Jabor A, Kazda A, Figge J. Diagnosis of metabolic acid-base disturbances in critically ill patients. Am J Respir Crit Care Med. 2000 Dec;162(6):2246-51. doi: 10.1164/ajrccm.162.6.9904099. — View Citation

Ferrer M, Sellares J, Valencia M, Carrillo A, Gonzalez G, Badia JR, Nicolas JM, Torres A. Non-invasive ventilation after extubation in hypercapnic patients with chronic respiratory disorders: randomised controlled trial. Lancet. 2009 Sep 26;374(9695):1082-8. doi: 10.1016/S0140-6736(09)61038-2. Epub 2009 Aug 12. — View Citation

Forsythe SM, Schmidt GA. Sodium bicarbonate for the treatment of lactic acidosis. Chest. 2000 Jan;117(1):260-7. doi: 10.1378/chest.117.1.260. — View Citation

From AM, Bartholmai BJ, Williams AW, Cha SS, Pflueger A, McDonald FS. Sodium bicarbonate is associated with an increased incidence of contrast nephropathy: a retrospective cohort study of 7977 patients at mayo clinic. Clin J Am Soc Nephrol. 2008 Jan;3(1):10-8. doi: 10.2215/CJN.03100707. Epub 2007 Dec 5. — View Citation

Gunnerson KJ, Saul M, He S, Kellum JA. Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients. Crit Care. 2006 Feb;10(1):R22. doi: 10.1186/cc3987. — View Citation

Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, Saint S, Schaeffer AJ, Tambayh PA, Tenke P, Nicolle LE; Infectious Diseases Society of America. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010 Mar 1;50(5):625-63. doi: 10.1086/650482. — View Citation

Husain FA, Martin MJ, Mullenix PS, Steele SR, Elliott DC. Serum lactate and base deficit as predictors of mortality and morbidity. Am J Surg. 2003 May;185(5):485-91. doi: 10.1016/s0002-9610(03)00044-8. — View Citation

Ichai C, Massa H, Hubert S. c. In: SAS EM, editor. EMC Anesthésie-Réanimation. Paris; 2006.

Jaber S, Jung B, Sebbane M, Ramonatxo M, Capdevila X, Mercier J, Eledjam JJ, Matecki S. Alteration of the piglet diaphragm contractility in vivo and its recovery after acute hypercapnia. Anesthesiology. 2008 Apr;108(4):651-8. doi: 10.1097/ALN.0b013e31816725a6. — View Citation

Jung B, Rimmele T, Le Goff C, Chanques G, Corne P, Jonquet O, Muller L, Lefrant JY, Guervilly C, Papazian L, Allaouchiche B, Jaber S; AzuRea Group. Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. A prospective, multiple-center study. Crit Care. 2011;15(5):R238. doi: 10.1186/cc10487. Epub 2011 Oct 13. — View Citation

Kellum JA, Levin N, Bouman C, Lameire N. Developing a consensus classification system for acute renal failure. Curr Opin Crit Care. 2002 Dec;8(6):509-14. doi: 10.1097/00075198-200212000-00005. — View Citation

Kellum JA, Song M, Almasri E. Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis. Chest. 2006 Oct;130(4):962-7. doi: 10.1378/chest.130.4.962. — View Citation

Kellum JA, Song M, Venkataraman R. Effects of hyperchloremic acidosis on arterial pressure and circulating inflammatory molecules in experimental sepsis. Chest. 2004 Jan;125(1):243-8. doi: 10.1378/chest.125.1.243. — View Citation

Kellum JA. Clinical review: reunification of acid-base physiology. Crit Care. 2005 Oct 5;9(5):500-7. doi: 10.1186/cc3789. Epub 2005 Aug 5. — View Citation

Kellum JA. Disorders of acid-base balance. Crit Care Med. 2007 Nov;35(11):2630-6. doi: 10.1097/01.CCM.0000286399.21008.64. — View Citation

Kelly AM, Dwamena B, Cronin P, Bernstein SJ, Carlos RC. Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy. Ann Intern Med. 2008 Feb 19;148(4):284-94. doi: 10.7326/0003-4819-148-4-200802190-00007. Erratum In: Ann Intern Med. 2008 Aug 5;149(3):219. — View Citation

Kraut JA, Kurtz I. Metabolic acidosis of CKD: diagnosis, clinical characteristics, and treatment. Am J Kidney Dis. 2005 Jun;45(6):978-93. doi: 10.1053/j.ajkd.2005.03.003. — View Citation

Kraut JA, Kurtz I. Use of base in the treatment of acute severe organic acidosis by nephrologists and critical care physicians: results of an online survey. Clin Exp Nephrol. 2006 Jun;10(2):111-7. doi: 10.1007/s10157-006-0408-9. — View Citation

Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol. 2010 May;6(5):274-85. doi: 10.1038/nrneph.2010.33. Epub 2010 Mar 23. — View Citation

Laffey JG, O'Croinin D, McLoughlin P, Kavanagh BP. Permissive hypercapnia--role in protective lung ventilatory strategies. Intensive Care Med. 2004 Mar;30(3):347-56. doi: 10.1007/s00134-003-2051-1. Epub 2004 Jan 14. — View Citation

Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993 Dec 22-29;270(24):2957-63. doi: 10.1001/jama.270.24.2957. Erratum In: JAMA 1994 May 4;271(17):1321. — View Citation

Mathieu D, Neviere R, Billard V, Fleyfel M, Wattel F. Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical study. Crit Care Med. 1991 Nov;19(11):1352-6. doi: 10.1097/00003246-199111000-00008. — View Citation

Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren DK. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Jul 1;49(1):1-45. doi: 10.1086/599376. Erratum In: Clin Infect Dis. 2010 Apr 1;50(7):1079. Dosage error in article text. Clin Infect Dis. 2010 Feb 1;50(3):457. — View Citation

Morimoto Y, Morimoto Y, Kemmotsu O, Alojado ES. Extracellular acidosis delays cell death against glucose-oxygen deprivation in neuroblastoma x glioma hybrid cells. Crit Care Med. 1997 May;25(5):841-7. doi: 10.1097/00003246-199705000-00021. — View Citation

RENAL Replacement Therapy Study Investigators; Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009 Oct 22;361(17):1627-38. doi: 10.1056/NEJMoa0902413. — View Citation

Shah SN, Abramowitz M, Hostetter TH, Melamed ML. Serum bicarbonate levels and the progression of kidney disease: a cohort study. Am J Kidney Dis. 2009 Aug;54(2):270-7. doi: 10.1053/j.ajkd.2009.02.014. Epub 2009 Apr 25. — View Citation

Smith I, Kumar P, Molloy S, Rhodes A, Newman PJ, Grounds RM, Bennett ED. Base excess and lactate as prognostic indicators for patients admitted to intensive care. Intensive Care Med. 2001 Jan;27(1):74-83. doi: 10.1007/s001340051352. — View Citation

Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med. 1998 Nov;26(11):1793-800. doi: 10.1097/00003246-199811000-00016. — View Citation

* Note: There are 38 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Composite criteria of Day 28 mortality and/or patients with at least one organ failure defined as a SOFA score of 3 or 4 Composite criteria of Day 28 mortality and/or patients with at least one organ failure defined as a SOFA score of 3 or 4 Day 0 to Day 28
Secondary Evolution of the organ failure scores use of SOFA score to assess the outcome 2 Day 0 to Day 28
Secondary Duration of renal replacement therapy (days) need to renal replacement therapy Day 0 to Day 28
Secondary Duration of mechanical ventilation and ventilatory free days (days) duration of mechanical ventilation and ventilatory free days Day 0 to Day 28
Secondary Duration of vasopressors administration (h) need for vasopressors and fluids using duration of vasopressor infusion (D0 to D28) Day 0 to Day 28
Secondary Hospital acquired infections (incidence) hospital acquired infections using United States Centers for Disease Control definitions and a dedicated document Day 0 to Day 28
Secondary Amount of intravenous fluid (ml) Day 0 to Day 2
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