Clinical trial NCT02501213: Evaluation of the Efficacy of Diuretics for Symptomatic Malignant Ascites Episodes in Advanced Stage of Cancer (DIASC)
Official title: A Randomized Cross-over Trial Evaluating the Efficacy of Diuretics for Symptomatic Malignant Ascites Episodes in Advanced Palliative Stage of Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cancer
Keywords: Diuretic
Malignant ascites
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
First posted: 2015-07-17
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: While some authors recommend diuretics as the first treatment to initiate for symptoms caused by malignant ascites (MA), their prescription is variable. No randomized, controlled study has assessed their benefit in this context. According to literature, diuretics may bring relief in about 40% of cases, regardless of primary tumor.

The purpose of our study is to assess the effectiveness of diuretic treatment according to Serum Ascites Albumin Gradient (SAAG) measured before treatment. Judgment criteria is the time elapsed between recurrent MA that requires paracentesis. The investigators will also examine whether SAAG and serum levels of renin and aldosterone can predict symptom response to diuretics.

Detailed description: Patients eligible for the trial and having signed their consent to participate will be randomized to arm A or B.

Treatment order is randomly attributed to patients at the 1st paracentesis, after the reception of the laboratory results necessary to evaluate SAAG value. Randomization is stratified 1:1 according to SAAG values (≥ or \< to 11g/L) and Systemic treatment (yes or not)

* Patients randomized to arm A will be observed until the next episode requiring paracentesis (due to clinical symptoms : abdominal pain or heaviness, dyspnoea, orthopnoea, nausea/vomiting, anorexia, early satiety, gastro-oesophageal reflux, lower limb and genital oedema), at which time they will receive arm B (diuretics), in absence of contra-indication to diuretic treatment.
* Patients randomized to arm B will receive diuretics until the next episode requiring paracentesis, at which time they will receive arm A (observation).

Patients will have a physical assessment within 24 hours prior to the start of treatment, once every two weeks for patients randomized in arm A and each week for patients randomized in arm B, at cross-over and at the end of the study. Patient will also have a biological assessment within 24 hours prior to the start of treatment, twice a week for patients randomized in arm B, at cross-over and at the end of the study. Finally, they will address a quality of life questionnaire (QLQ-C15-PAL) prior to the start of treatment, at cross-over and at the end of the study.

Eligibility criteria: Inclusion Criteria:

* Patients with advanced stage cancer
* First episode of malignant ascites
* Grade 2 or 3 ascites
* Clinically symptomatic ascites requiring paracentesis due to : abdominal pain or heaviness, dyspnoea, orthopnoea, nausea/vomiting, anorexia, early satiety, gastro-oesophageal reflux, lower limb and genital oedema
* Age ≥ 18 years
* Performance status ≤ 3
* Life expectancy ≥ 1 month
* Absence of contra-indication to diuretic treatment
* Patient regularly followed up by a palliative care or supportive care team
* Signed and dated informed consent

Exclusion Criteria:

* Hepatic disorders : cirrhosis, hepatitis, hepatocellular insufficiency, hepatic encephalopathy
* Non malignant ascites
* Hydroelectrolytic disorders: hyponatremia (\< 130 mmol/L) or hyperkaliemia (\> 5 mmol/L) or severe hypokaliemia (\< 3 mmol/L)
* Functional acute renal insufficiency
* Urinary disorders : Obstruction in the urinary tract, Oliguria/anuria
* Chronic renal failure
* Patient unable to swallow
* Sulfamides allergy
* Hypersensitivity to spironolactone or to any of the excipients
* Hypersensitivity to furosemide or to any of the excipients
* Pregnant or breastfeeding women
* Patient under guardianship

Primary outcomes:
measure: Time between symptomatic malignant ascites episodes requiring paracentesis
timeFrame: Patients will be followed until their third malignant ascites episode, an expected average of 30 days.
Secondary outcomes:
measure: Tolerance
timeFrame: Up to 30 days after the last administration of the product
measure: Quality of life based on the EORTC (European Organization for Research and Treatment of Cancer) QLQ-C15-PAL
timeFrame: At baseline (prior to the start of treatment)
measure: Quality of life based on the EORTC (European Organization for Research and Treatment of Cancer) QLQ-C15-PAL
timeFrame: At cross-over (approximately 15 days after inclusion)
measure: Quality of life based on the EORTC (European Organization for Research and Treatment of Cancer) QLQ-C15-PAL
timeFrame: At the end of the study (up to 6 months).
measure: Description of the patterns of prescription of diuretics
timeFrame: During randomization in arm B (that is to say during approximately 15 days between the first and the second or between the second and the third milgnant ascites episode).
measure: Predictive factors of response to diuretics : Serum Ascites Albumin Gradient (SAAG)
timeFrame: Within 24 hours prior to the start of treatment
measure: Predictive factors of response to diuretics : renin aldosterone plasmatic level
timeFrame: Within 24 hours prior to the start of treatment
measure: Predictive factors of response to diuretics : SAAG
timeFrame: Twice a week for patients randomized in arm B
measure: Predictive factors of response to diuretics : renin aldosterone plasmatic level
timeFrame: Twice a week for patients randomized in arm B
measure: Predictive factors of response to diuretics : SAAG
timeFrame: At cross-over (approximately 15 days after inclusion)
measure: Predictive factors of response to diuretics : renin aldosterone plasmatic level
timeFrame: At cross-over (approximately 15 days after inclusion)
measure: Predictive factors of response to diuretics : SAAG
timeFrame: At the end of the study (up to 6 months).
measure: Predictive factors of response to diuretics : renin aldosterone plasmatic level
timeFrame: At the end of the study (up to 6 months).
Other outcomes:
Locations:
city: Compiègne
country: France
facility: Centre Hospitalier Intercommunal Compiègne-Noyon
city: Grande Synthe
country: France
facility: Polyclinique de Grande Synthe
city: Lille
country: France
facility: CHRU Lille
city: Lille
country: France
facility: Hôpital Saint Vincent de Paul
city: Lille
country: France
facility: Centre Oscar Lambret
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hôpital Jean Jaurès
city: Paris
country: France
facility: GH Diaconesses Croix St Simon
city: Pierre-Bénite
country: France
facility: Hôpital Lyon Sud
city: Reims
country: France
facility: Institut Jean Godinot
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Tourcoing
country: France
facility: Centre Hospitalier Tourcoing
city: Valenciennes
country: France
facility: Polyclinique Vauban
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Oscar Lambret
name: Vincent GAMBLIN, MD
role: PRINCIPAL_INVESTIGATOR
References: