Role of Acetazolamide and Hydrochlorothiazide Followed by Furosemide in Treating Nephrotic Edema

Acetazolamide and Hydrochlorothiazide Followed by Furosemide Versus Hydrochlorothiazide and Furosemide Followed by Furosemide for the Treatment of Adults With Refractory Nephrotic Edema: A Randomized, Double-Blind Trial

The purpose of this study is to determine whether using furosemide following acetazolamide is effective in treating refractory edema associated with nephrotic syndrome.

Study Overview

• Status: Completed
• Conditions: Edema; Nephrotic Syndrome
• Intervention / Treatment: Drug: Acetazolamide and Hydrochlorothiazide Followed by Furosemide; Drug: Furosemide and Hydrochlorothiazide Followed by Furosemide

Detailed Description

Edema is referred to increase in interstitial fluid that is clinically evident. The main causes of generalized edema are heart failure, renal failure, nephrotic syndrome, glomerulonephritis and chronic liver failure. In some cases, edema is treated by management of the underlying disease. However, in some other cases edema may persist and become more severe that needs adjuvant treatments. Because use of diuretics such as furosemide and hydrochlorothiazide is not completely effective in treating severe refractory edema, use of some other diuretics is also recommended. In this double-blind clinical trial, weight and some lab data including blood urea nitrogen, serum creatinine, serum sodium, serum potassium, serum albumin, urine sodium, urine potassium, 24-hour urine volume, 24-hour urine protein and 24-hour urine creatinine of 20 random adult patients with nephrotic syndrome who have refractory edema and GFR>60 ml/min/1.73m2 and are referred to nephrology clinic of Shiraz University of Medical Sciences will be measured; the patients should not have hypokalemia and other causes of edema such as heart failure or cirrhosis. Then the patients are divided into 2 groups with 10 members in each. The first group will be prescribed 40 mg of furosemide and 50 mg of hydrochlorothiazide and the second one will receive 250 mg of acetazolamide and 50 mg of hydrochlorothiazide daily for 1 week. Then, weight and mentioned lab data will be measured again. After that, all the patients will have 40 mg of furosemide daily for 2 weeks. Then, weight and mentioned lab data will be measured for one more time.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Having refractory edema due to nephrotic syndrome
2. Having GFR>60 ml/min/1.73m2
3. Being able to come for weekly visit
4. Having the minimum age of 18 years
5. Signing the informed consent form

Exclusion Criteria:

1. Hypokalemia
2. Pregnancy
3. Renal transplant
4. active malignancy or infection
5. acidosis
6. Using NSAIDs
7. Having another causes of edema including liver cirrhosis, heart failure
8. Neurologic or psychiatric problem hindering adherence to the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acetazolamide; Each patient receives 250 mg of acetazolamide and 50 mg of hydrochlorothiazide daily for 1 week. Then they are prescribed 40 mg of furosemide daily for 2 weeks.	Drug: Acetazolamide and Hydrochlorothiazide Followed by Furosemide; Other Names: Diamox Sequels and Microzide Followed by Lasix
Active Comparator: Furosemide; Each patient is prescribed 40 mg of furosemide and 50 mg of hydrochlorothiazide daily for 1 week. Then they receive 40 mg of furosemide daily for 2 weeks.	Drug: Furosemide and Hydrochlorothiazide Followed by Furosemide; Other Names: Lasix and Microzide Followed by Lasix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in weight at the end of third week	Baseline and at the end of the third week

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in systolic and diastolic blood pressure at the end of third week	Baseline and at the end of the third week
Change from baseline in serum sodium at the end of third week	Baseline and at the end of the third week
Change from baseline in serum potassium at the end of third week	Baseline and at the end of the third week
Change from baseline in blood urea nitrogen at the end of third week	Baseline and at the end of the third week
Change from baseline in serum creatinine at the end of third week	At the start and at the end of the third week
Change from baseline in serum albumin at the end of third week	Baseline and at the end of the third week
Change from baseline in urine sodium at the end of third week	Baseline and at the end of the third week
Change from baseline in urine potassium at the end of third week	Baseline and at the end of the third week
Change from baseline in 24-hour urine volume at the end of third week	Baseline and at the end of the third week
Change from baseline in 24-hour urine creatinine at the end of third week	Baseline and at the end of the third week
Change from baseline in 24-hour urine protein at the end of third week	Baseline and at the end of the third week

Collaborators and Investigators

• Sponsor: Shiraz University of Medical Sciences
• Investigators: Study Chair: Mohammad Mahdi Sagheb, MD, Nephrologist at Shiraz University of Medical Science

Publications and helpful links

General Publications

• Soleimani M. A novel target for diuretic therapy. Iran J Kidney Dis. 2012 Nov;6(6):419-25.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: April 20, 2015
• First Submitted That Met QC Criteria: April 22, 2015
• First Posted (Estimate): April 28, 2015

Study Record Updates

• Last Update Posted (Estimate): February 23, 2016
• Last Update Submitted That Met QC Criteria: February 21, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Acetazolamide; Edema; Furosemide; Nephrotic syndrome
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Edema; Nephrotic Syndrome; Nephrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Anticonvulsants; Sodium Chloride Symporter Inhibitors; Sodium Potassium Chloride Symporter Inhibitors; Acetazolamide; Hydrochlorothiazide; Furosemide
• Other Study ID Numbers: 7308