Trial Outcomes & Findings for Acetazolamide in Decompensated Heart Failure With Volume OveRload (ADVOR) (NCT NCT03505788)

NCT ID: NCT03505788

Last Updated: 2024-10-28

Results Overview

defined as the absence of signs of volume overload, within 3 days after randomization and with no indication for escalation of decongestive therapy.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 519 participants
• Primary outcome timeframe: 4 days
• Results posted on: 2024-10-28

Participant Flow

Participant milestones

Measure	Placebo In the placebo group, the patient will receive the standard of care loop diuretics and the placebo	Acetazolamide In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide
Overall Study STARTED	260	259
Overall Study COMPLETED	257	254
Overall Study NOT COMPLETED	3	5

Reasons for withdrawal

Measure	Placebo In the placebo group, the patient will receive the standard of care loop diuretics and the placebo	Acetazolamide In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide
Overall Study Lost to Follow-up	2	1
Overall Study Withdrawal by Subject	1	3
Overall Study Physician Decision	0	1

Baseline Characteristics

Acetazolamide in Decompensated Heart Failure With Volume OveRload (ADVOR)

Baseline characteristics by cohort

Measure	Placebo n=260 Participants In the placebo group, the patient will receive the standard of care loop diuretics and the placebo.	Acetazolamide n=259 Participants In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide.	Total n=519 Participants Total of all reporting groups
Age, Continuous	78.5 Years STANDARD_DEVIATION 8.8 • n=5 Participants	77.9 Years STANDARD_DEVIATION 9.0 • n=7 Participants	78.2 Years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	105 Participants n=5 Participants	89 Participants n=7 Participants	194 Participants n=5 Participants
Sex: Female, Male Male	155 Participants n=5 Participants	170 Participants n=7 Participants	325 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	256 Participants n=5 Participants	258 Participants n=7 Participants	514 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Ischaemic aetiology	113 Participants n=5 Participants	119 Participants n=7 Participants	232 Participants n=5 Participants
Weight	84.4 kg STANDARD_DEVIATION 19.7 • n=5 Participants	85.3 kg STANDARD_DEVIATION 23 • n=7 Participants	84.8 kg STANDARD_DEVIATION 21.4 • n=5 Participants
Heart rate	77 bpm STANDARD_DEVIATION 18 • n=5 Participants	79 bpm STANDARD_DEVIATION 19 • n=7 Participants	78 bpm STANDARD_DEVIATION 18 • n=5 Participants
Systolic blood pressure	127 mmHg STANDARD_DEVIATION 22 • n=5 Participants	126 mmHg STANDARD_DEVIATION 20 • n=7 Participants	127 mmHg STANDARD_DEVIATION 21 • n=5 Participants
Diastolic blood pressure	73 mmHg STANDARD_DEVIATION 13 • n=5 Participants	72 mmHg STANDARD_DEVIATION 13 • n=7 Participants	72 mmHg STANDARD_DEVIATION 13 • n=5 Participants
Congestion score	4 units on a scale n=5 Participants	4 units on a scale n=7 Participants	4 units on a scale n=5 Participants
Composite of volume assessment score - Edema	241 Participants n=5 Participants	237 Participants n=7 Participants	478 Participants n=5 Participants
Composite of volume assessment score - Pleural Effusion	143 Participants n=5 Participants	130 Participants n=7 Participants	273 Participants n=5 Participants
Composite of volume assessment score - Ascites	25 Participants n=5 Participants	21 Participants n=7 Participants	46 Participants n=5 Participants
Maintenance dose - furosemide equivalent	60 mg n=5 Participants	80 mg n=7 Participants	60 mg n=5 Participants
LVEF	43 % STANDARD_DEVIATION 15 • n=5 Participants	43 % STANDARD_DEVIATION 15 • n=7 Participants	43 % STANDARD_DEVIATION 15 • n=5 Participants
Proportion LVEF ≤ 40%	111 Participants n=5 Participants	113 Participants n=7 Participants	224 Participants n=5 Participants
NT-proBNP	6483 pg/mL n=5 Participants	5600 pg/mL n=7 Participants	6173 pg/mL n=5 Participants
NYHA II	35 Participants n=5 Participants	31 Participants n=7 Participants	66 Participants n=5 Participants
NYHA III	148 Participants n=5 Participants	148 Participants n=7 Participants	296 Participants n=5 Participants
NYHA IV	77 Participants n=5 Participants	80 Participants n=7 Participants	157 Participants n=5 Participants
Serum hemoglobin	11.9 g/dL STANDARD_DEVIATION 2.0 • n=5 Participants	11.9 g/dL STANDARD_DEVIATION 2.0 • n=7 Participants	11.9 g/dL STANDARD_DEVIATION 2.0 • n=5 Participants
Sodium	140 mmol/L STANDARD_DEVIATION 4 • n=5 Participants	139 mmol/L STANDARD_DEVIATION 4 • n=7 Participants	139 mmol/L STANDARD_DEVIATION 4 • n=5 Participants
Serum creatinine	1.5 mg/dL n=5 Participants	1.5 mg/dL n=7 Participants	1.5 mg/dL n=5 Participants
eGFR	38 mL/min/1.73m^3 n=5 Participants	40 mL/min/1.73m^3 n=7 Participants	39 mL/min/1.73m^3 n=5 Participants
eGFR < 60mL/min/1.73m^3	215 Participants n=5 Participants	209 Participants n=7 Participants	424 Participants n=5 Participants
Comorbidities - History of atrial fibrillation	189 Participants n=5 Participants	187 Participants n=7 Participants	376 Participants n=5 Participants
Comorbidities - Diabetes	133 Participants n=5 Participants	112 Participants n=7 Participants	245 Participants n=5 Participants
Comorbidities - Hypertension	207 Participants n=5 Participants	182 Participants n=7 Participants	389 Participants n=5 Participants
Use of ACEi/ARB/ARNi	140 Participants n=5 Participants	130 Participants n=7 Participants	270 Participants n=5 Participants
Beta-blocker	212 Participants n=5 Participants	207 Participants n=7 Participants	419 Participants n=5 Participants
MRA	103 Participants n=5 Participants	113 Participants n=7 Participants	216 Participants n=5 Participants
ICD	41 Participants n=5 Participants	38 Participants n=7 Participants	79 Participants n=5 Participants
CRT	25 Participants n=5 Participants	36 Participants n=7 Participants	61 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 days

defined as the absence of signs of volume overload, within 3 days after randomization and with no indication for escalation of decongestive therapy.

Outcome measures

Measure	Placebo n=259 Participants In the placebo group, the patient will receive the standard of care loop diuretics and the placebo	Acetazolamide n=256 Participants In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide
Successful Decongestion	79 Participants	108 Participants

SECONDARY outcome

Timeframe: 3 months

All-cause mortality during the first 3 months after start of the study

Outcome measures

Measure	Placebo n=259 Participants In the placebo group, the patient will receive the standard of care loop diuretics and the placebo	Acetazolamide n=256 Participants In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide
Mortality	31 Participants	39 Participants

SECONDARY outcome

Timeframe: 3 months

If a patient is readmitted to the hospital within 3 months, this data will be collected

Outcome measures

Measure	Placebo n=259 Participants In the placebo group, the patient will receive the standard of care loop diuretics and the placebo	Acetazolamide n=256 Participants In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide
Hospital Readmission	45 Participants	47 Participants

SECONDARY outcome

Timeframe: 3 months

The time frame between hospital admission and discharge will be calculated

Outcome measures

Measure	Placebo n=259 Participants In the placebo group, the patient will receive the standard of care loop diuretics and the placebo	Acetazolamide n=256 Participants In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide
Length of Index Hospital Admission	9.9 days Interval 9.1 to 10.8	8.8 days Interval 8.0 to 9.5

SECONDARY outcome

Timeframe: at baseline, day 4 (or discharge), at 3 months

A questionnaire about the patients' quality of life will be performed at baseline, the morning of day 4, at any readmission, 3 months. The questionnaire is divided into 5 levels of severity with a score varying from 1 to 5. 1 indicates no problems and 5 indicates severe problems. The EQ-5D-5L health status, defined by the EQ-5D-5L descriptive system, are converted into a single index value (utility data). Values are anchored at 1 (full health) and 0 (a state as bad as being dead) as required by their use in economic evaluation. Values less than 0 represent health states regarded as worse than a state that is as bad as being dead.

Outcome measures

Measure	Placebo n=258 Participants In the placebo group, the patient will receive the standard of care loop diuretics and the placebo	Acetazolamide n=259 Participants In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide
EuroQoL Five Dimensions Questionnaire (EQ-5D) Baseline	0.571 score on a scale Standard Deviation 0.027	0.546 score on a scale Standard Deviation 0.027
EuroQoL Five Dimensions Questionnaire (EQ-5D) Day 4 (or discharge)	0.688 score on a scale Standard Deviation 0.028	0.656 score on a scale Standard Deviation 0.028
EuroQoL Five Dimensions Questionnaire (EQ-5D) 3 months FU	0.592 score on a scale Standard Deviation 0.028	0.546 score on a scale Standard Deviation 0.028

Adverse Events

Placebo

Serious events: 124 serious events

Other events: 184 other events

Deaths: 31 deaths

Acetazolamide

Serious events: 123 serious events

Other events: 192 other events

Deaths: 39 deaths

Serious adverse events

Measure	Placebo n=259 participants at risk In the placebo group, the patient will receive the standard of care loop diuretics and the placebo	Acetazolamide n=256 participants at risk In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide
Cardiac disorders Cardiac disorders	30.9% 80/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	31.2% 80/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Renal and urinary disorders Renal and urinary disorders	5.8% 15/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	7.8% 20/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Blood and lymphatic system disorders Blood and lymphatic system disorders	0.77% 2/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	1.2% 3/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Endocrine disorders Endocrine disorder	0.00% 0/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	0.39% 1/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Gastrointestinal disorders Gastrointestinal disorders	1.5% 4/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	2.0% 5/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
General disorders General disorders and administration site conditions	1.5% 4/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	1.6% 4/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Hepatobiliary disorders Hepatobiliary disorders	0.39% 1/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	0.39% 1/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Infections and infestations Infections and infestations	8.5% 22/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	9.8% 25/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	1.2% 3/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	1.2% 3/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Metabolism and nutrition disorders Metabolism and nutrition disorders	1.5% 4/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	1.2% 3/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	0.39% 1/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	0.78% 2/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	1.5% 4/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	2.7% 7/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Nervous system disorders Nervous system disorders	0.77% 2/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	0.00% 0/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Product Issues Product issues	0.39% 1/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	0.00% 0/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Psychiatric disorders Psychiatric disorders	0.39% 1/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	0.00% 0/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	0.77% 2/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	2.7% 7/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Surgical and medical procedures Surgical and medical procedures	0.77% 2/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	0.00% 0/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Vascular disorders Vascular disorders	3.1% 8/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	1.2% 3/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).

Other adverse events

Measure	Placebo n=259 participants at risk In the placebo group, the patient will receive the standard of care loop diuretics and the placebo	Acetazolamide n=256 participants at risk In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide
Cardiac disorders Cardiac arrhythmia	11.6% 30/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	11.3% 29/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Cardiac disorders Decreased and nonspecific blood pressure disorders and shock	5.4% 14/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	7.8% 20/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
Cardiac disorders Heart failure	32.0% 83/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	27.0% 69/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
General disorders Hyperkaelemia	7.3% 19/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	5.5% 14/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).
General disorders Hypokaelemia	14.7% 38/259 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).	23.4% 60/256 • Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).

Additional Information

Prof. dr. Wilfried Mullens

Ziekenhuis Oost-Limburg

Phone: +32(0)89327140

Email: wilfried.mullens@zol.be

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place