The BASE Study: Bicarbonate Administration to Stabilize Estimated Glomerular Filtration Rate (eGFR)

• Sponsor: Jennifer Gassman, PhD (Other)
• Overall Status: Completed
• CT.gov ID: NCT02521181
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), The Cleveland Clinic (Other)
• Enrollment: 194
• Locations: 7
• Arms: 3
• Actual Duration (Months): 32
• Patients Per Site: 27.7
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The two doses of sodium bicarbonate being tested are 0.5 and 0.8 mEq/kg-lean body weight (LBW) per day. Sodium bicarbonate, also known as baking soda, may help prevent kidney failure in people with chronic kidney disease. However, the dose to prescribe in order to test this possibility in a clinical trial is uncertain. The BASE pilot clinical trial will help determine the best dose of sodium bicarbonate to prescribe in a future study that will test the long-term safety and efficacy of sodium bicarbonate as a treatment to preserve kidney function in individuals with chronic kidney disease.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Drug: Lower Dose Sodium Bicarbonate; Drug: Higher Dose Sodium Bicarbonate; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 194 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Other
• Official Title: The BASE Study: Bicarbonate Administration to Stabilize eGFR
• Actual Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Jan 1, 2018
• Actual Study Completion Date: Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lower Dose Sodium Bicarbonate Participants will receive oral 0.5 milliequivalents (mEq)/kg-lean body weight (LBW)/day of sodium bicarbonate. Half of the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.)	Drug: Lower Dose Sodium Bicarbonate; Lower dose oral Sodium Bicarbonate (0.5 milliequivalents (mEq)/kg-LBW/day)
Experimental: Higher Dose Sodium Bicarbonate Participants will receive 0.8 mEq/kg-LBW/day of sodium bicarbonate. Half the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.)	Drug: Higher Dose Sodium Bicarbonate; Higher dose oral Sodium Bicarbonate (0.8 mEq/kg-LBW/day)
Placebo Comparator: Placebo Participants will take the same number of placebo capsules as if they were assigned to receive either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of sodium bicarbonate. Half the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.)	Drug: Placebo; Oral placebo equivalent to either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of Sodium Bicarbonate

Outcome Measures

Primary Outcome Measures

1. Number of Participants in Each Dose Arm Prescribed (i) Full Randomized Sodium Bicarbonate Dose at End of 28 Weeks & (ii) at Least 25% of Randomized Sodium Bicarbonate Dose at End of 28 Weeks as a Proportion of the Number Randomized to That Group [Baseline, 28 weeks]

   The prescribed dose for each participant at the end of 28 weeks will be determined by the safety and tolerability of each dose during the intervention period. The primary assessments will examine the percentage of participants in each dose arm who are prescribed (i) the full randomized sodium bicarbonate dose according to the protocol at the end of 28 weeks and (ii) at least 25% of the randomized sodium bicarbonate dose according to the protocol at the end of 28 weeks. The two doses of sodium bicarbonate being tested are 0.5 and 0.8 mEq/kg-lean body weight per day.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Serum bicarbonate 20-28 mEq/L at screening (the average of the two most recent values in Baseline must be 20-28 mEq/L prior to randomization)

2. Moderate to severe chronic kidney disease (CKD) at the time of screening, defined as one of the following:

• eGFR 20-44 ml/min/1.73m2 or

• eGFR 45-59 ml/min/1.73m2 plus random urinary albumin:creatinine (ACR) ≥100 mg/gm

1. Blood pressure <160/100 mm Hg at screening (must be <150/100 mm Hg prior to randomization)

2. Lean body weight 38.0-96.0 kg at the time of screening

3. Age allowing legal consent without parental involvement (18-21 years, depending on individual state regulations)

4. Able to provide consent

5. Able to travel to study visits

6. Able to read English

7. In the opinion of the site investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations

8. In the opinion of the site investigator, medically stable

Exclusion Criteria:

1. Use of chronic daily oral alkali (such as sodium bicarbonate, sodium citrate, potassium citrate, etc) with one exception: calcium carbonate ≤1500 mg/day is allowed, as some will take this for the indication of bone health

2. On five or more antihypertensive and/or diuretic agents, regardless of the indication

3. Serum potassium <3.3 or ≥5.5 mEq/L at screening (must be 3.5-5.5 mEq/L prior to randomization)

4. Self-reported vegetarian

5. New York Heart Association Class 3 or 4 heart failure symptoms, known left ventricular ejection fraction ≤30%, or hospital admission for heart failure within the past 3 months

6. Frequent urinary tract infections (≥2 in the past year)

7. Presence of indwelling urinary catheter or urinary conduit (such as neobladder or urostomy)

8. Factors judged to limit adherence to interventions (e.g., alcoholism, history of missing clinic visits, chronic gastrointestinal disorder that makes compliance with the intervention unreliable)

9. Organ transplant recipients (excluding cornea)

10. Active glomerular disease requiring or potentially requiring immunosuppressive treatment

11. Chronic immunosuppressive therapy (for ≥3 months) for any indication. This does not include oral steroids <10 mg per day, inhaled steroids, or topical steroids

12. Anticipated initiation of dialysis or kidney transplantation within 12 months as assessed by the site investigator

13. Current participation in another interventional research study

14. Malignancy requiring therapy within 2 years (basal or squamous cell skin carcinoma and localized prostate cancer are exempted)

15. Pregnancy or planning to become pregnant or currently breast-feeding. Women of childbearing potential (pre-menopausal and not surgically sterilized) will have urine pregnancy test before enrollment.

16. Life expectancy <12 months as determined by the site investigator

17. Institutionalized individuals, including prisoners and nursing home residents

18. Plans to leave the immediate area within the next 12 months

19. Routinely leaves town for multiple weeks each year such that protocol visits would be missed

20. Chronic use of supplemental oxygen

21. Use of both angiotensin-converting-enzyme inhibitor (ACEI) and Angiotensin II Receptor Blockers (ARBs)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Denver Nephrology Research	Denver	Colorado	United States	80230
2	George Washington University	Washington	District of Columbia	United States	20037
3	Northwestern University	Chicago	Illinois	United States	60611
4	Data Coordinating Center; Cleveland Clinic Foundation; Quantitative Health Sciences; 9500 Euclid Avenue	Cleveland	Ohio	United States	44195-5196
5	Baylor/Scott & White	Temple	Texas	United States	76502
6	University of Utah	Salt Lake City	Utah	United States	84112
7	Utah VA	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• Jennifer Gassman, PhD
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• The Cleveland Clinic

Investigators

• Study Director: Michael F. Flessner, MD, PhD, DKUHD, NIDDK, NIH
• Study Director: John W. Kusek, PhD, DKUHD, NIDDK, NIH
• Study Chair: Linda Fried, MD, MPH, VA Pittsburgh Healthcare System

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 12, 2016

More Information

Publications

None provided.

• Responsible Party: Jennifer Gassman, PhD, Principal Investigator-Data Coordinating Center, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT02521181
• Other Study ID Numbers: DK099877-B; U01DK099877
• First Posted: Aug 13, 2015
• Last Update Posted: Oct 20, 2020
• Last Verified: Oct 1, 2020

• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic

Study Results

Participant Flow

Recruitment Details	Patients were recruited from the CKD medical clinic patients of the recruiting centers.

Arm/Group Title	Lower Dose Sodium Bicarbonate	Higher Dose Sodium Bicarbonate	Placebo
Arm/Group Description	Participants will receive oral 0.5 milliequivalents (mEq)/kg-lean body weight (LBW)/day of sodium bicarbonate. Half of the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.) Lower Dose Sodium Bicarbonate: Lower dose oral Sodium Bicarbonate (0.5 milliequivalents (mEq)/kg-LBW/day)	Participants will receive 0.8 mEq/kg-LBW/day of sodium bicarbonate. Half the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.) Higher Dose Sodium Bicarbonate: Higher dose oral Sodium Bicarbonate (0.8 mEq/kg-LBW/day)	Participants will take the same number of placebo capsules as if they were assigned to receive either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of sodium bicarbonate. Half the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.) Placebo: Oral placebo equivalent to either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of Sodium Bicarbonate
Period Title: Overall Study
STARTED	52	90	52
COMPLETED	52	90	52
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Lower Dose Sodium Bicarbonate	Higher Dose Sodium Bicarbonate	Placebo	Total
Arm/Group Description	Participants will receive oral 0.5 milliequivalents (mEq)/kg-lean body weight (LBW)/day of sodium bicarbonate. Half of the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.) Lower Dose Sodium Bicarbonate: Lower dose oral Sodium Bicarbonate (0.5 milliequivalents (mEq)/kg-LBW/day)	Participants will receive 0.8 mEq/kg-LBW/day of sodium bicarbonate. Half the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.) Higher Dose Sodium Bicarbonate: Higher dose oral Sodium Bicarbonate (0.8 mEq/kg-LBW/day)	Participants will take the same number of placebo capsules as if they were assigned to receive either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of sodium bicarbonate. Half the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.) Placebo: Oral placebo equivalent to either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of Sodium Bicarbonate	Total of all reporting groups
Overall Participants	52	90	52	194
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	20 38.5%	39 43.3%	15 28.8%	74 38.1%
>=65 years	32 61.5%	51 56.7%	37 71.2%	120 61.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.9 (14.0)	67.3 (10.8)	66.2 (10.8)	66.6 (11.7)
Sex: Female, Male (Count of Participants)
Female	21 40.4%	29 32.2%	13 25%	63 32.5%
Male	31 59.6%	61 67.8%	39 75%	131 67.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 11.5%	8 8.9%	3 5.8%	17 8.8%
Not Hispanic or Latino	46 88.5%	82 91.1%	49 94.2%	177 91.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	2 2.2%	1 1.9%	3 1.5%
Asian	3 5.8%	3 3.3%	2 3.8%	8 4.1%
Native Hawaiian or Other Pacific Islander	1 1.9%	1 1.1%	0 0%	2 1%
Black or African American	17 32.7%	27 30%	23 44.2%	67 34.5%
White	28 53.8%	55 61.1%	26 50%	109 56.2%
More than one race	1 1.9%	1 1.1%	0 0%	2 1%
Unknown or Not Reported	2 3.8%	1 1.1%	0 0%	3 1.5%
Region of Enrollment (participants) [Number]
United States	52 100%	90 100%	52 100%	194 100%
CKD Stage (Count of Participants)
Stage 3A (eGFR 45-60)	9 17.3%	17 18.9%	4 7.7%	30 15.5%
Stage 3B (eGFR 30-45)	30 57.7%	46 51.1%	31 59.6%	107 55.2%
Stage 4 (eGFR 15-30)	13 25%	27 30%	17 32.7%	57 29.4%
Diabetes Mellitus (Count of Participants)
Count of Participants [Participants]	27 51.9%	53 58.9%	25 48.1%	105 54.1%
History of Heart Disease (Count of Participants)
Count of Participants [Participants]	18 34.6%	28 31.1%	20 38.5%	66 34%
Congestive Heart Failure (Count of Participants)
Count of Participants [Participants]	5 9.6%	8 8.9%	7 13.5%	20 10.3%
COPD (Count of Participants)
Count of Participants [Participants]	4 7.7%	6 6.7%	0 0%	10 5.2%
Smoking Status (Count of Participants)
Never	26 50%	47 52.2%	25 48.1%	98 50.5%
Former Smoker	15 28.8%	39 43.3%	25 48.1%	79 40.7%
Current Smoker	11 21.2%	4 4.4%	2 3.8%	17 8.8%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	96.1 (25.8)	95.4 (22.4)	93.6 (20.3)	95.1 (22.7)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	32.8 (8.43)	32.8 (7.87)	31.6 (5.92)	32.5 (7.54)
Lean Body Mass (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	58.4 (10.7)	58.4 (9.84)	58.7 (9.44)	58.5 (9.91)
Systolic BP (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	127 (13.7)	127 (12.3)	127 (13.0)	127 (12.8)
Ace/ARB Use (Count of Participants)
Count of Participants [Participants]	40 76.9%	60 66.7%	35 67.3%	135 69.6%
eGFR (ml/min/1.73m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ml/min/1.73m^2]	36.5 (9.56)	36.4 (9.60)	34.5 (8.59)	35.9 (9.32)
Urine Albumin / Creatinine Ratio (g/mg) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [g/mg]	222	176	147	181
Serum Bicarbonate (meq/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meq/L]	24.2 (2.25)	24.2 (2.38)	23.8 (2.17)	24.1 (2.28)
Serum Potassium (meq/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meq/L]	4.5 (0.4)	4.4 (0.4)	4.5 (0.5)	4.5 (0.4)
Urinary Ammonium (mmol/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/day]	19.3 (10.5)	22.0 (12.2)	20.5 (13.2)	20.9 (12.0)
Urinary PH (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.86 (0.46)	5.75 (0.46)	5.81 (0.56)	5.80 (0.49)
Estimated DIetary Protein Intake (g/day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/day]	73.3 (25.4)	81.9 (30.5)	79.1 (29.5)	78.8 (29.0)

Outcome Measures

1. Primary Outcome

Title	Number of Participants in Each Dose Arm Prescribed (i) Full Randomized Sodium Bicarbonate Dose at End of 28 Weeks & (ii) at Least 25% of Randomized Sodium Bicarbonate Dose at End of 28 Weeks as a Proportion of the Number Randomized to That Group
Description	The prescribed dose for each participant at the end of 28 weeks will be determined by the safety and tolerability of each dose during the intervention period. The primary assessments will examine the percentage of participants in each dose arm who are prescribed (i) the full randomized sodium bicarbonate dose according to the protocol at the end of 28 weeks and (ii) at least 25% of the randomized sodium bicarbonate dose according to the protocol at the end of 28 weeks. The two doses of sodium bicarbonate being tested are 0.5 and 0.8 mEq/kg-lean body weight per day.
Time Frame	Baseline, 28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lower Dose Sodium Bicarbonate	Higher Dose Sodium Bicarbonate	Placebo
Arm/Group Description	Participants will receive oral 0.5 milliequivalents (mEq)/kg-lean body weight (LBW)/day of sodium bicarbonate. Half of the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.) Lower Dose Sodium Bicarbonate: Lower dose oral Sodium Bicarbonate (0.5 milliequivalents (mEq)/kg-LBW/day)	Participants will receive 0.8 mEq/kg-LBW/day of sodium bicarbonate. Half the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.) Higher Dose Sodium Bicarbonate: Higher dose oral Sodium Bicarbonate (0.8 mEq/kg-LBW/day)	Participants will take the same number of placebo capsules as if they were assigned to receive either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of sodium bicarbonate. Half the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.) Placebo: Oral placebo equivalent to either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of Sodium Bicarbonate
Measure Participants	52	90	52
Number of Patients Completing on Full Dose	50 96.2%	78 86.7%	45 86.5%
Num of Patients Completing on >= 25% of Full Dose	51 98.1%	82 91.1%	48 92.3%

Adverse Events

Time Frame	32 Weeks
Arm/Group Title	Lower Dose Sodium Bicarbonate		Higher Dose Sodium Bicarbonate		Placebo
Arm/Group Description	Participants will receive oral 0.5 milliequivalents (mEq)/kg-lean body weight (LBW)/day of sodium bicarbonate. Half of the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.) Lower Dose Sodium Bicarbonate: Lower dose oral Sodium Bicarbonate (0.5 milliequivalents (mEq)/kg-LBW/day)		Participants will receive 0.8 mEq/kg-LBW/day of sodium bicarbonate. Half the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.) Higher Dose Sodium Bicarbonate: Higher dose oral Sodium Bicarbonate (0.8 mEq/kg-LBW/day)		Participants will take the same number of placebo capsules as if they were assigned to receive either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of sodium bicarbonate. Half the total daily dose is taken in the morning and the other half is taken in the evening. (If the number of capsules is an odd number, the greater number of capsules will be taken in the morning.) Placebo: Oral placebo equivalent to either 0.5 mEq/kg-LBW/day or 0.8 mEq/kg-LBW/day of Sodium Bicarbonate
All Cause Mortality
	Lower Dose Sodium Bicarbonate		Higher Dose Sodium Bicarbonate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/90 (0%)		1/52 (1.9%)
Serious Adverse Events
	Lower Dose Sodium Bicarbonate		Higher Dose Sodium Bicarbonate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/52 (9.6%)		16/90 (17.8%)		7/52 (13.5%)
Cardiac disorders
Cardiovascular Hospitalizations	1/52 (1.9%)	1	3/90 (3.3%)	3	2/52 (3.8%)	2
Endocrine disorders
Endocrine Disorder Hospitalizations	0/52 (0%)	0	1/90 (1.1%)	1	0/52 (0%)	0
Gastrointestinal disorders
Gastrointestinal Hospitalizations	2/52 (3.8%)	2	3/90 (3.3%)	3	0/52 (0%)	0
Injury, poisoning and procedural complications
Infection Hospitalizations	0/52 (0%)	0	1/90 (1.1%)	1	1/52 (1.9%)	2
Injury Hospitalizations	0/52 (0%)	0	0/90 (0%)	0	1/52 (1.9%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal Hospitalizations	1/52 (1.9%)	1	5/90 (5.6%)	5	0/52 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignancy Hospitalizations	0/52 (0%)	0	1/90 (1.1%)	1	0/52 (0%)	0
Psychiatric disorders
Psychiatric Hospitalizations	1/52 (1.9%)	2	0/90 (0%)	0	1/52 (1.9%)	1
Renal and urinary disorders
Reached ESRD (Dialysis or Transplant)	0/52 (0%)	0	1/90 (1.1%)	1	0/52 (0%)	0
Renal Hospitalizations	1/52 (1.9%)	1	1/90 (1.1%)	1	1/52 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory Hospitalizations	0/52 (0%)	0	1/90 (1.1%)	1	1/52 (1.9%)	1
Vascular disorders
Vascular Hospitalizations	0/52 (0%)	0	1/90 (1.1%)	1	0/52 (0%)	0
Other (Not Including Serious) Adverse Events
	Lower Dose Sodium Bicarbonate		Higher Dose Sodium Bicarbonate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/52 (76.9%)		74/90 (82.2%)		42/52 (80.8%)
Gastrointestinal disorders
Severe gastrointestinal symptoms	9/52 (17.3%)	15	16/90 (17.8%)	28	5/52 (9.6%)	6
Moderate gastrointestinal symptoms	7/52 (13.5%)	17	22/90 (24.4%)	36	13/52 (25%)	17
Mild gastrointestinal symptoms	24/52 (46.2%)	54	36/90 (40%)	107	24/52 (46.2%)	62

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.