Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USA
Introduction Diabetic ketoacidosis (DKA) is a potentially life-threatening diabetic complication. Despite the high prevalence of DKA and the substantial associated healthcare burden, limited research on strategies to improve outcomes currently exists.Thiamine (vitamin B1) is a cofactor of pyruvate d...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-02-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/14/2/e077586.full |
| _version_ | 1827323689329229824 |
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| author | Ari Moskowitz Michael W Donnino Anne V Grossestreuer Katherine M Berg Long Ngo Xiaowen Liu Jacob Vine Shivani Mehta Lakshman Balaji Noa Berlin Meredith Shea |
| author_facet | Ari Moskowitz Michael W Donnino Anne V Grossestreuer Katherine M Berg Long Ngo Xiaowen Liu Jacob Vine Shivani Mehta Lakshman Balaji Noa Berlin Meredith Shea |
| author_sort | Ari Moskowitz |
| collection | DOAJ |
| description | Introduction Diabetic ketoacidosis (DKA) is a potentially life-threatening diabetic complication. Despite the high prevalence of DKA and the substantial associated healthcare burden, limited research on strategies to improve outcomes currently exists.Thiamine (vitamin B1) is a cofactor of pyruvate dehydrogenase, which plays a key role in aerobic glucose metabolism. Thiamine deficiency is common in patients with DKA, resulting in a shift to anaerobic metabolism and hyperlactatemia, which can prolong and complicate recovery. Therefore, we hypothesise that thiamine administration will improve aerobic metabolism and lead to faster resolution of acidemia in patients with DKA.Methods and analysis In this single centre, double-blind, randomised, placebo-controlled, parallel group interventional trial, 100 patients admitted to the hospital with DKA will be randomised to receive either intravenous thiamine (200 mg in 50 mL 0.9% saline) or placebo (0.9% saline identical in appearance and volume) two times per day for 2 days. The primary outcome will be the change in bicarbonate level over 24 hours as compared between the two treatment groups. Additional secondary outcomes include the change over time in anion gap, lactate levels, oxygen consumption by circulating mononuclear cells, intensive care unit and hospital length-of-stay and hospital resource usage when comparing the two study arms.Ethics and dissemination This trial was approved by the Committee on Clinical Investigations, the institutional review board of Beth Israel Deaconess Medical Center (protocol number 2018P000475). Findings will be disseminated through peer-reviewed publications and professional conference presentations.Trial registration number NCT03717896; clinicaltrials.gov. |
| first_indexed | 2024-03-07T19:11:55Z |
| format | Article |
| id | doaj.art-0ad714e2efaa482fad6386d9cc2d3364 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-04-25T01:55:58Z |
| publishDate | 2024-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-0ad714e2efaa482fad6386d9cc2d33642024-03-07T16:20:08ZengBMJ Publishing GroupBMJ Open2044-60552024-02-0114210.1136/bmjopen-2023-077586Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USAAri Moskowitz0Michael W Donnino1Anne V Grossestreuer2Katherine M Berg3Long Ngo4Xiaowen Liu5Jacob Vine6Shivani Mehta7Lakshman Balaji8Noa Berlin9Meredith Shea10Montefiore Medical Center, New York, New York, USABeth Israel Deaconess Medical Center, Boston, Massachusetts, USABeth Israel Deaconess Medical Center, Boston, Massachusetts, USABeth Israel Deaconess Medical Center, Boston, Massachusetts, USABeth Israel Deaconess Medical Center, Boston, Massachusetts, USABeth Israel Deaconess Medical Center, Boston, Massachusetts, USABeth Israel Deaconess Medical Center, Boston, Massachusetts, USABeth Israel Deaconess Medical Center, Boston, Massachusetts, USABeth Israel Deaconess Medical Center, Boston, Massachusetts, USABeth Israel Deaconess Medical Center, Boston, Massachusetts, USABeth Israel Deaconess Medical Center, Boston, Massachusetts, USAIntroduction Diabetic ketoacidosis (DKA) is a potentially life-threatening diabetic complication. Despite the high prevalence of DKA and the substantial associated healthcare burden, limited research on strategies to improve outcomes currently exists.Thiamine (vitamin B1) is a cofactor of pyruvate dehydrogenase, which plays a key role in aerobic glucose metabolism. Thiamine deficiency is common in patients with DKA, resulting in a shift to anaerobic metabolism and hyperlactatemia, which can prolong and complicate recovery. Therefore, we hypothesise that thiamine administration will improve aerobic metabolism and lead to faster resolution of acidemia in patients with DKA.Methods and analysis In this single centre, double-blind, randomised, placebo-controlled, parallel group interventional trial, 100 patients admitted to the hospital with DKA will be randomised to receive either intravenous thiamine (200 mg in 50 mL 0.9% saline) or placebo (0.9% saline identical in appearance and volume) two times per day for 2 days. The primary outcome will be the change in bicarbonate level over 24 hours as compared between the two treatment groups. Additional secondary outcomes include the change over time in anion gap, lactate levels, oxygen consumption by circulating mononuclear cells, intensive care unit and hospital length-of-stay and hospital resource usage when comparing the two study arms.Ethics and dissemination This trial was approved by the Committee on Clinical Investigations, the institutional review board of Beth Israel Deaconess Medical Center (protocol number 2018P000475). Findings will be disseminated through peer-reviewed publications and professional conference presentations.Trial registration number NCT03717896; clinicaltrials.gov.https://bmjopen.bmj.com/content/14/2/e077586.full |
| spellingShingle | Ari Moskowitz Michael W Donnino Anne V Grossestreuer Katherine M Berg Long Ngo Xiaowen Liu Jacob Vine Shivani Mehta Lakshman Balaji Noa Berlin Meredith Shea Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USA BMJ Open |
| title | Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USA |
| title_full | Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USA |
| title_fullStr | Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USA |
| title_full_unstemmed | Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USA |
| title_short | Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USA |
| title_sort | thiamine as adjunctive therapy for diabetic ketoacidosis dkat trial protocol and statistical analysis plan a prospective single centre double blind randomised placebo controlled clinical trial in the usa |
| url | https://bmjopen.bmj.com/content/14/2/e077586.full |
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