Efficacy of Oral Acetazolamide as Add-on Diuretic Therapy in Decongestion in Patients With Heart Failure and Diuretic Resistance

This is a 1:1 ratio single center, double-blind, RCT on the diuretic and decongestive effects of oral acetazolamide in Iranian patients with HF. This study will be conducted on heart failure patients whose symptoms of congestion are not relieved by oral diuretics and are temporarily hospitalized in a section called the infusion ward and receive intravenous diuretics. The infusion unit is a separate unit where patients with heart failure who are not adequately relieved by oral diuretics are admitted for a short period of time and receive injectable furosemide. In this study, 250 mg acetazolamide tablets and placebo and furosemide 20 mg will be used. The medical information of the patients will be recorded, patients' clinical status will be evaluated by calculating the EVEREST score at baseline and third day , the weight and laboratory indices will also be measured at baseline and third day based on the same scale and fixed laboratory kits, respectively. Blood pressure will be also measured by an expert nurse at the baseline and each day before the furosemide injection by the same blood pressure cuff. Patients will be followed for clinical events to day 90. The protocol was drafted according to the standard protocol items for clinical trials) SPIRIT) guideline for randomized clinical trial protocols.

Study objectives The main objective is to determine the effect of oral acetazolamide and furosemide, as a loop diuretic, combination therapy on improvement of the congestion in patients at baseline and third day. Urinary sodium to creatinine ratio is an indicator in this objective and will be measured at 2 P.M. in these days.

Prespecified secondary objectives included the following: N-terminal pro B-type natriuretic peptide (NT-proBNP) level on the 30th day, the hospitalization rate in a three-month period, comparison of quality of life between two groups at the end of the third month and change in weight, creatinine level, urinary sodium excretion, potassium level, and hematological indices in complete blood count (CBC) at third day of the trial. At the end of the third month, we will assess our patients' quality of life using the Iranian Heart Failure Quality of Life (IHFQoL) Questionnaire. The validity and reliability of this questionnaire, which has 16 questions in 5 dimentions, has been confirmed by Naderi et al in 2012. (Kornbach's alpha coefficient= 0.922) .This questionnaire offers a range of total scores between 20 and 66. The items are scored on a three- or four-point Likert scale, with a higher score indicating a better quality of life for the individual. These are the five dimensions that are the subject of this survey: severity of disease symptoms (items 1, 2, 3, 4, 6), physical limitations (items 7-1 to 7-6), mental limitations (items 5, 9, 11), social aspects (items 8, 10, 12, 13), self-care (items 14, 15) and the patient's overall satisfaction (item 16). (16)